U of WM Tom Yin Grant Documents Part 1

Notice of Award
RESEARCH Issue Daie: 11/13/2009

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Department of Health and Human Services
National Institutes of Health
NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
Grant Number: 2R01DC007177-06
Principallnvestlgator(s):
TOM C.T. YIN, PHD
Project Title: Behavioral and physiological studies of sound localization
Award e-mailed to: NIH@rsp.wisc.edu
Budget Period: 12/01/2009 -11/30/2010

Project Period: 12101/2004 -11/30/2014
Dear Business Official:
The National Institutes of Health hereby awards a grant in the amount of $312,265 (see "Award
Calculation" in Section I and "Terms and Conditions" In Section III) to UNIVERSITY OF
WISCONSIN MADISON in support of the above referenced project. This award is pursuant to the
authority of 42 USC 241 42 CFR 52 and is subject to the requirements of this statute and regulation
and of other referenced, incorporated or attached terms and conditions.
Acceptance of this award including the "Terms and Conditions" is acknowledged by the grantee
when funds are drawn down or otherwise obtained from the grant payment system.
Each publication, press release or other document that cites results from NIH grant-supported
research must Include an acknowledgment of NIH grant support and disclaimer such as "The
project described was supported by Award Number R01DC007177 from the National Institute On
Deafness And Other Communication Disorders. The content Is solely the responsibility of the
authors and does not necessarily represent the official views of the National Institute On Deafness
And Other Communication Disorders or the National Institutes of Health."
AWard recipients are required to comply with the NIH Public Access Policy. This includes
submission to PubMed Central (PMC), upon acceptance for publication, an electronic version of a
final peer-reviewed, manUscript resulting from research supported in whole or in part, with direct
costs from National Institutes of Health. The author's final peer-reviewed manuscript is defined as
the final version accepted for journal publication, and Includes all modifications from the publishing
peer review process. For additional information, please visit http://publicaccess.nih.gov/.
Award recipients must promote objectivity in research by establishing standards to ensure that the
design, conduct and reporting of research funded under NIH-funded awards are not biased by a
confiicting financial interest of an Investigator. Investigator is defined as the Principal Investigator
and any other person who is responsible for the design, conduct, or reporting of NIH-funded
research or proposed research, including the Investigator's spouse and dependent children.
Awardees must have a written administrative process to identify and manage financial conflict of
interest and must inform Investigators of the conflict of Interest policy and of the Investigators'
responsibilities. Prior to expenditure of these awarded funds, the Awardee must report to the NIH
Awarding Component the existence of a conflicting interest and within 60 days of any new
conflicting interests identified after the initial report. Awardees must comply with these and all other
aspects of 42 CFR Part 50, Subpart F. These requirements also apply to subgrantees, contractors,
or collaborators engaged by the Awardee under this award. The NIH website
http://grants.nih.gov/grants/policy/coiflndex.htm provides additional information.
2011-04-22 000003
If you have any questions about this award, please contact the individual(s) referenced in Section
IV.
Sincerely yours,
Christopher Myers
Grants Management Officer
NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
Additional information follows
Page-2
2011-04-22 000004
SECTION 1- AWARD DATA - 2R01DC007177·06
AWard Calculation (U.S. Dollars)
Federal Direct Costs $212,500

Federal F&A Costs $99,765
Approved Budget $312,265
Federal Share $312,265
TOTAL FEDERAL AWARD AMOUNT $312,265
AMOUNT OF THIS ACTION (FEDERAL SHARE) $312,265
~I TOTALS FOR ALL

YR THIS JlWJlRn r.11 ATIVE TOTALS
'?"'~ 112~
112,21
112,21
9 !,265 S312,265
10 i312,265 :'I1? ?"'''
,~ouu"""o"uoJfutureyeartotalcostsupport, to the I _, offunds and '"
progress of the project
Fiscal Information:
iEDA Number:
Document Number: RbCOo 77B

Fiscal Year: 2010
CAN 2010 2011 2013 2014

424501 312,265 312,265 312,265 312,265
Recommended future year total cost support, subject to the availability of funds and satisfactory
progress of the project
NIH Administrative Data:

PCC: HR61 1 OC: 414B 1 Processed: MYERSC 11/09/2009
SECTION 11- PAYMENT/HOTLINE INFORMATION - 2R01DC007117·06
For payment and HHS Office of Inspector General Hotline Information, see the NIH Home Page at
http·/Igrants_nih.gov/grants/policyJawardconditions.htm
SECTION 111- TERMS AND CONDITIONS - 2R01DC007177·06
This award Is based on the application submitted to, and as approved by, NIH on the above·titled
project and is subject to the terms and conditions incorporated either directly or by reference in the
following:
a. The grant program legislation and program regulation cited in this Notice of Award.
b. Conditions on activities and expenditure of funds in other statutory requirements, such as
those included in appropriations acts.
c. 45 CFR Part 74 or 45 CFR Part 92 as applicable.
d. The NIH Grants Policy Statement, including addenda in effect as of the beginning date of
the budget period.
e. This award notice, INCLUDING THE TERMS AND CONDITIONS CITED BELOW.
(See NIH Home Page at 'http://grants.nlh.gov/grants/policy/awardconditions.htm' for certain

references cited above.)
This institution is a signatory to the Federal Demonstration Partnership (FOP) Phase V Agreement
which requires active institutional participation in new or ongoing FOP demonstrations and pilots.
Page-3
2011-04-22 000005
An unobligated balance may be carried over into the next budget period without Grants
Management Officer prior approval.
This grant is subject to Streamlined Noncompeting Award Procedures (SNAP).
In accordance with P.L. 110-161, compliance with the NIH Public Access Policy is now mandatory.
For more information, see NOT-OD-08-033 and the Public Access website:
http://publicaccess.nih.gov/.
Treatment of Program Income:

Additional Costs
SECTION IV - DC Special Terms and Conditions - 2R01DC007177-06
This is a Modular Grant Award without direct cost categorical breakdowns issued in accordance
with the guidelines published in the NIH Grants Policy Statement, December 2003, see
(http://grants.nlh.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm - 30c54600227). Recipients
are required to allocate and account for costs related to this award by category within their
institutional accounting system in accordance with applicable cost principles.
STAFF CONTACTS
The Grants Management Specialist is responsible for the negotiation, award and administration of
this project and for interpretation of Grants Administration policies and provisions. The Program
Official is responsible for the scientific, programmatic and technical aspects of this project. These
individuals work together in overall project administration. Prior approval requests (signed by an
Authorized Organizational Representative) should be submitted in writing to the Grants
Management Specialist. Requests may be made via e-mail.
Grants Management Specialist: Castilla Mcnamara

Email: mcnamara@nidcd.nlh.govPhone: (301)435-1407 Fax: (301)402-1758
Program Official: Christopher Platt

Email: plattc@nidcd.nih.govPhone:(301)496-1804 Fax: (301)402-6251
SPREADSHEET SUMMARY
GRANT NUMBER: 2R01DC007177-06
INSTITUTION: UNIVERSITY OF WISCONSIN MADISON
Facilities and Year 6 Year 7 Year 8 Year 9 . Year 10

Administrative
Costs
F&A Cost Rate ~8.5% 8.5% 48.5% 8.5% 48.5%
1
F&A Cost Base fl>205,700 ~205,700 $205,700 ~205,700 fl>205,700
1
F&A Costs 1 $99,765 99,765 $99,765 $99,765 $99,765
Page-4
2011-04-22 000006
OTHER SUPPORT
YIN, TOM C.T.
L6?(I~ ~,,+ L 09/01/07-04/0109

,
(Co-PI; C . 'J ]' $69,740
Feasibility studies using bilateral cochlear implants in cats
This grant supports a pilot project to explore the possibility of sound localization in deafened cats who are
implanted with bilateral cochlear implants. We hope to get enough preliminary data to support an R01
application to NIH.
'There is no effort by the Pion this grant. Monies received by the Co-PI help to fund a research assistantship
for a graduate student.
R90 DK071515 (Yin PI) 09/30/04-07/31/09' .0 calendar months

NIH/NIDDKD $16,784
Training Program in Clinical Neuroengineering
'Grant is in no-cost extension until 07/30/10
T90 DK070079 (Yin PI)

NIH/NIDDKD
09/30/04-07/31/09'
$227,173
o calendar months
Training Program in Clinical Neuroengineering
'Grant is in no-cost extension until 07/30/10

" There is no effort by the Pion this training grant. Monies received fund research assistantships for trainees.
PENDING
None
OVERLAP
None
2011-04-22 000007
Just In Time Report
ReportsobmiHed on: 11/051200911:07 AM
IRB Confirmation: No IRS Certification was required
Human Subjects Education: No Human Subjects Education was provided
IACUC Confirmation: 10/2212008
Page 1
2011-04-22 000008
PI: YIN, TOM C.T. Title: Behavioral and physiological studies of sound localization
Received: 03/04/2009 FOA: PA07-070 Council: 10/2009
Competition 10: ADOBE-FORMS-A FDA Title: RESEARCH PROJECT GRANT (PARENT R01)
2 R01 OCOO7177-06 Dual: Accession Number: 3145120
IPF: 578503 Organization: UNIVERSITY OF WISCONSIN MADISON
Former Number: Department: PHYSIOLOGY
IRG/SRG: AUO AIDS:N Expedited: N
Subtotal Direct Costs Animals:Y New Investigator: N

(excludes consortium F&A) Humans: N Early Stage Investigator: N
Year 6: 250,000 Clinical Trial: N
Year 7: 250,000 Current HS Code: 10
Year 8: 250,000 HESC:N
Year 9: 250,000
Year 10: 250,000
Senior/Key Personnel: Organization: Role Category:
TOM YIN The Board of Regents of the UW System PDIPI
Stephen Lomber University Of Western Ontario Other (Specify)-OSC
Lloyd Minor Johns Hopkins University Other (Specify)-OSC
Additions for Review
Other publishedlaccepted 05/1212009

manuscripts
Updated Pages publishedlaccepted 05/1212009

manuscripts
2011-04-22 000009
APPLICATION FOR FEDERAL ASSISTANCE 2. DATE SUBMITTED Applicant Identifier
SF 424 (R&R) I 03/04/2009

I I I
3. DATE RECEIVED BY STATE State Application Identifier
1.' TYPE OF SUBMISSION
I I I I
o Pre-application [gJ Application o Changed/Corrected Application 4. Federal Identifier IDC007177
I
5. APPLICANT INFORMATION "Organizational DUNS: 1161202122 I
• Legal Name: IThe Board of Regents of the UW System
I
Department: I
I
Division: I I
, Streetl: 121 N. Park Street
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Street2: /suite 6401 I
'" City: !Madison I Counly: IDane
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'" State: WI: Wisconsin Provine,,, I
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'Country: I USA: UNITED STATES I 'ZIP I Postal Code: 153715-1218 I
Person to be contacted on matters involving this application
Prefix: I
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' First Name: 1itZ--=:J I
Middle Name: [J- I I
, Last Name: 1,\_ "
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Suffix: I
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, Phone Number: It R J I Fax Number: : C ,J:: \ I
Email: [t, $ --.. I
6.' EMPLOYER IDENTIFICATION @fJor(TlN}: f \ I
7•• TYPE OF APPLICANT: L H: Public/State Controlled Institution of Higher Education I
Other (Specify): I
I
Small Business Organization Type o Women Owned D Socially and Economically Disadvantaged
8.• TYPE OF APPLICATION: If Revision, mark appropriate box(es).
o New oResubmission OA. Increase Award 0 B. Decrease Award DC. Increase Duration 00. Decrease Duration
[gJ Renewal o Continuation o Revision DE. Other (speCify):1 I
,. Is this application being submitted to other agencies? Yeso No[gJ What other Agencies? I
I
g •• NAME OF FEDERAL AGENCY: , 10. CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER:I
I National Institutes of Health I TITLE: Research project Grant (Parent ROl)
11 •• DESCRIPTIVE TITLE OF APPLICANT'S PROJECT:

IBehaVioral and physiological studies of sound localization
12.' AREAS AFFECTED BY PROJECT (cities, counties, statas, etc.) 13. PROPOSED PROJECT: 14. CONGRESSIONAL DISTRICTS OF:
I
IN/A
* Start Date * Ending Date a.' Applicant b, * Project
I
I 12/01/2009 II 11/30/2014 112 ] 1002 I
15. PROJECT DIRECTOR/PRINCIPAL INVESTIGATOR CONTACT INFORMATION
Prefix: lor. I
' First Name: ITOM
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Middle Name: Ie T
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, Last Name: IYIN
I Suffix: I I
PositionfTitle: IPROFESSOR I
* Organization Name: IThe Board of Regents of the UW System
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Department:!PHYSIOLOGY I Division: IMedicine and Public Health I
* Street1: 11300 UNIVERSITY AVE I
Street2: 1290B MEDICAL SCIENCES CTR I
* City: IMADISON I County: loane
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* State:
I WI: Wisconsin I
Province: I I
'Country: I USA: UNITED STATES I ' ZIP I Poslal Code: 153706-1509
I
* Phone Number:!6082620368 I
Fax Number: 16082655512 I
* Email: IYIN@PHYSIOLOGY.t'HSc.EDU I
Tracking Number:GRANTI0194930
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'''11) Expiration Data: 0413012008
Funding Opportunity Number:PA-07-070 Received Date:2009-03-04T1S:42:32-04:00
2011-04-22 000010
SF 424 (R&R) APPLICATION FOR FEDERAL ASSISTANCE Page 2
16. ESTIMATED PROJECT FUNDING 17. 'IS APPLICATION SUBJECT TO REVIEW BY STATE EXECUTIVE
ORDER 12372 PROCESS?
a. YES 0 THIS PREAPPLICATION/APPLICATION WAS MADE

a. 'Tolal Estimaled ProJecl Funding 11,836,850.00 I. AVAILABLE TO THE STATE EXECUTIVE ORDER 12372
b.• Tolal Federal & Non·Federal Funds \1, 836, 850.00 I PROCESS FOR REVIEW ON:
c. 'Eslimaled Program Income ..,10'-'"."'00"--_ _ _ _ _ _-11 DATE: I I
1
b. NO ~ PROGRAM IS NOT COVERED BY E.O. 12372; OR
o PROGRAM
REVIEW
HAS NOT BEEN SELECTED BY STATE FOR
18. By signing this application, I certify (1) to the statements contained in the list of certifications'" and (2) that the statements herein are
true, complete and accurate to the best of my knowledge. I also provide the required assurances'" and agree to comply with any
resulting terms if I accept an award. I am aware that any false, fictitious, or fraudulent statements or claims may subject me to
criminal, civil, or administrative penalties. (U.S. Code, Title 18, Section 1001)
~ 'Iagree
* The list of certifications and assurances, or an Internet sIte where you may obtain this I/st, Is contained in the announcement or agency specific Instructions.
19. Authorized Representatlv~.~-:-:--:---;~_=;~====::::r-~~~~_ _-,

Prefix: ' r.::::> I E;iName: I . ) ( ] I ~
Middle Name: ( I ]
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Lasl Name: I X -
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'Counlry: I .... -c: I 'ZIP 1 Poslal Code: Il:.-:..·_ _ I
It Phone Number: I. \ I/!,ax Number: I
* Email: !preaward@rsp.wise.edu I
* Signature of Authorized Representative * Date Signed
I I 03/04/2009
20. Pr.-appllcalion I 1 Add Allaehnient 1 Del"leAliacl1!]1.nll;Vi.wi>.II~Ctll;'enl ·1

21. Attach an additional list of Project Congressional Districts if needed.
1 1-· Add AIi"ehmenl 1 Pelele A«achtnent 1 ViewAliachmanl J
OMB Number: 4040·0001
Expiration Dale: 04/30/2008
Tracking Number:GRANTl0194930 Funding Opportunity Number:PA·07·070 Received Date:2009·03·04T15:42:32·04:OO
2011-04-22 000011
Principal Investigator/Program Director (Last, first, middle): YIN, TOM, C T
424 R&R and PHS·398 Specific

Page Numbers
Table Of Contents
SF 424 R&R Face Page .. ···•····••·· .. •·········•···•·······•···•··•···•·· •....•.........•......•...•.....•..•••
Table of Contents·············································· .............................................. . 3
Performance Sites·········· .. ·····•······ .. ··•··•··•.. ······•···· .. ··· ....................................... . 4
Research & Related Other Project Information········································ ..•·• ................... .. 5
Project Summary/Abstract (Description)··································· .... • 6
Public Health Relevance Statement (Narrative attachment)················ ..•·••··••·········•···• 7
Facilities & Other Resources···················· .. ·······•·•···••··• 8
Equipment········································ 9
Research & Related Senior/Key Person················································........................ .. 12
Biographical Sketches for each listed Senior/Key Person·································_· .. ·· 14
PHS 398 Specific Cover Page Supplement········· ..•···•••·•···•·••·····•·•···· .. ····· •...........•.•........•.. 25
PHS 398 Specific Modular Budget····················· ..•···•••····•···•·····•··•· ............................. . 27
Personnel Justification·· .. ··•··••······ .. ···•••·····•••··••··• . 30
PHS 398 Specific Research Plan····················· ..•···········•··••····•·••.. ··............................ 31
Specific Aims······················.. · ..············• 32
Background & Significance··········· ....•·•·•·•••·· ..•·••········ 33
Preliminary Studies/Progress······················ .. ·· .. ·•·•••·••···· 40
Research Design & Methods··············.. ·· ..•····•··· .. ····•·••· 48
List of Publications························ .... ···•·•·····• 57
Vertebrate Animals········································ 59
Bibliography & References Cited······························..········ 60
Letters of Support········································ 67
PHS 398 Checklist············································· .........••.•••....•••.•....•••....••.••....•..• 69
Table of Contents Page 3
2011-04-22 000012
Principallnvestigator/Program Director (Last, first, middle): YIN, TOM, C T
RESEARCH & RELATED ProjecUPerformance Site Location(s)

Project/Performance Site Primary Location
Organization Name: IThe Board of Regents of the UW system

"Street1: 11300 University Avenue
Street2: ,
• City: IrM-'ad='=s=o=n============l,-=c:-o-un-:t-y:-,rD=a=ne======'----------,
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"State: I WI: Wisconsin Province: I

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. USA: UNITED STATES 1. .
Project/Performance Site Location 1

Organization Name: r ' - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - ,
'Streetl: =====================1
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Street2: -,:'============:;-==:r======'-------,
• City: ,- I County: 1
• State:~'==============:=!--=-=-=-=~'========;--;:P::ro:-v:;:in:::""-:-::-i'=='-------------,
• countryL:1',========US=A='=U=N='T=E=D=s=TA=T=E=s=========I-:·:-Z;.'I'P I Postal coLd:-e-:"'I==========="----,
Addtttonal Location(s) IL-_ _ _ _ _ _ _ _ _ _ _ _--' _:..:A.:.dd::..A..;.t:..:ta:..:c:..:hm:..:e"n:..:t--, Delete AHachment :Vi~l\'J Attachment I

OMB Number: 4040-0001
Expiration Date: 04/30/2008
Performance Sites Page 4
Tracking Number:GRANTl0194930 Funding Opportunity Number:PA-07-070 Received Date:2009-03-04TI 5:42:32-04:00

2011-04-22 000013
Princip-allnvesUgalor/P ogram Director (last, firsl, middle): YIN, TOM, C T
Close Form Print Page About -I
RESEARCH & RELATED Other Project Information
1. * Are Human Subjects Involved? 0 Yes ~No
1.a It YES to Human Subjects
Is the IRS review Pending? DYes
~~~~~
IRS Approval Date: LI_ _ _ _---.J

Exemption Number: 01 02 03 04 05 06
Human Subject Assurance Number: LI_ _ _ _ _ _ _---.J
2. * Are Vertebrate Animals Used? IZJ Yes

2.a. If YES to Vertebrate Animals
Is the IACUe review Pending? DYes ~No

IACUC Approval Date: LI~1!.lOu.I.£22"'1,-,2~O"O",8='-I_ _ _ _ _~
Animal Welfare Assurance Number ~IA"3",3",6,,8.::-,,O=.1_ _ _ _---,
3. * Is proprietary/privileged information included in the application? 0 Yes
4.a. * Does this project have an actual or potential impact on the environment? DYes ~No
4.b.ltyes, pleaseexPlaln:LI_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _--1
4.c. If this project has an actual or potential Impact on the environment, has an exemption been authorized or an environmental assessment (EA) or
environmental impact statement (EIS) been performed? 0
Yes No 0
4.d. If yes, please explain: LI_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _---.J
S.a. * Does this project involve activities outside the U.S. or partnership with International Collaborators? 0 Yes ~No
5.b.ltyes, Identifycountrie;s:.!:I=========================================~
S.c. Optional Explanation: LI_ _ -;=================:;-______ I
6." Project Summary/Abstract IAbstractl004884246.Pdf
~~---:--------;---------;---.J
Add Allachment- O~lele Att~chmend -'VJ~W I\ttachm~nt
7. * Project Narrative IPrOjectNarrativel004884247. pdf Add Attachment - f -D.elete__At1a--,~time.ntf Vfew-AU~,chm~nt,c_ 1
8. Bibliography & References Cited IBibliograPhYl004900942. pdf Add'AUa.chmenl I Dele'te'f\ttachment I Vievt'A,tachment
9. Facilities & Other Resources !Facilitiesl004884383 .pdf Add Attachment - I Delete A.ttachment.1 : View-At.t~.chm~l':It-
10. Equipment IEQUiPmentl004884385.Pdf Add AUachllJent I beleis Attachment I View Attachment
11. Other Attachments AdQAtlacl)ments Delete Attachments I View -Attachments ID

Expiration Date: 04/30/2008
Olher In(ormation PageS
Tracking Number:GRANTl0194930 Funding Opportunity Number: PA·07-070 Received Date:2009·03-04TJS:42:32-04:00
2011-04-22 000014
PROJECT SUMMARY
The overali aim of this project is to understand the neural mechanisms of sound localization. These results will
help us understand how the brain integrates auditory information from the two ears and produces orienting
movements of the head, eyes, and ears to allow close visual and auditory inspection of targets. The
experiments are designed to test the relative roles of two circuits that arise in the auditory brainstem to encode
the cues necessary to localize sounds and generate the motor programs that orient the head, eyes and ears to
the acoustic target. One circuit involves the midbrain nuclei of the inferior and superior colliculi with outputs to
motor Circuits in the brainstem from the deep layers of the superior colliculus. The other circuit involves
projections from the inferior colliculus to the medial geniculate and primary auditory cortex. By inactivating the
cortex or the midbrain, the relative roles of these two circuits in orienting behavior will be determined. The
second aim will examine the vestibulo-auricular reflex by testing for the reflex following inactivation of the
semicircular canals in the vestibular system. We will plug the semicircular canals and hypothesize that this will
greatly attenuate the reflex. In animals with mobile pinnae, it is hypothesized that the reflex serves to stabilize
the auditory world just like the vestibulo-ocular reflex stabilizes images on the retina in the presence of head
movements. The final aim will study the circuitry that moves the pinna as a model motor system and compare
it with the well-known oculomotor circuit. We will also examine the effect of immobilizing the pinna on sound
localization performance.
Project Description Page 6
2011-04-22 000015
Principallnvesligator/Program Director (Last, first. middle): YIN, TOM, C T
NARRATIVE
Spatial hearing is an important basic function of the auditory system. Defects in binaural function in human
patients can lead to considerable difficult yin understanding conversations in a noisy room, which is the most
common complaint of the hearing-impaired and can lead to severe social withdrawal.
Public Health Relevance Statement Page?
2011-04-22 000016
Principallnvesligator/Program Director (last, first, middle): YIN, TOM, C T
RESOURCES
________~_._J' re available for this

Laboratory: Three laboratories,l--S-beiovv.-____.!..-)f-
project. Please see detailed des\;npttons below. - .
.1>i---LLI'<u;!l.!!!!=L<U.!~~~JJ.LJ,l&.;!alJlJm!.!~re facilit{ x:-

It is run by expenenced staft under !tte SupetVislon of a
~""'-"""-"=~=JV1""==="""""'--,rn.,..-,,lccredited by the American Association for the Accreditation
Office: 75
computers i
rr
Computer: Please refer to detailed description below.
~
the P.1. and a 50 sq ft office for post-doc. Other post-doc and students have desks and
J
Facilities Page 8
2011-04-22 000017
Principallnvestigator/Program Direclor (Last, first, middle): YIN, TOM, C T
EQUIPMENT, ETC,
,{
.specifics' Tl:le Feseal'Gl:l-lal:l.Qratories are contained in three rooms in
;X:: ~
th~ *"
~~hiS·behavioral sound-localization laboratory contains a newly-installed double-walled, sound
insulated 60 th (Acoustic Systems, 7' x 10'), the insides of which have been lined with 4" Sonex foam. A S foot
=
magnetic search coil system (CNC Engineering) with three sets of phase detectors provide the ability to monitor
the orientations of three independent search coils (e.g. one each for eye, head and pinna movement) up to ±90
degrees. For data collection there is the usual array of electrophysiological recording equipment (BAK preamp,
window discriminator, and audio monitor), two Tektronix storage oscilloscopes for monitoring X-Y eye position and
neural activity. The sound proof booth also has an array of 32 speakers and LED's that can be mounted at any
one of 247 specific locations on a hemisphere at 10° increments. These are the sources of auditory and visual
stimuli.
There are 2 separate computer systems that use this setup.
The first one is a PC-based system (Deli Precision 650) for our single unit behavioral/physiology experiments.
This includes a set of devices from TDT (Tucker Davis Technologies) for stimulus generation, consisting of
2 RP2 processors (which replace our former Digital Stimulus System that ran on a MicroVAX II computer). The
RP2's provide auditory waveform generation including timing control, stimulus counting, envelope multipliers,
digital-to-analog converters, and the ability to synthesize sine waves with amplitude or frequency modulation.
Special waveforms (e.g. noise, speech, etc) stored in a dynamic RAM can be generated by repeatedly cycling
through that portion of RAM. Along with this there are 2 PA5 attenuators, 2 SA 1 power amplifiers, 4 PM2R power
multiplexers, an RV8 processor for speaker selection control, a PIS PCI interface, and Zbus racks, all from TDT
as well. For data collection there is a National Instruments AID board, a Keithley Instruments digital I/O board, a
Sheldon Instruments VC33 DSP for precise event timing, and a custom designed digital controller for selecting
one or more of the 32 tri-color LED's.
The second one consists of a PC system used for training cats, and includes the following equipment from TDT.
For stimulus generation there are 2 RP2 processors, speaker amplifiers, and a PIS PCI interface board, using
OpenEx and Open Developer software. For data collection there are TDT Medusa modules for multiunit
recording from the Michigan probes, including 1 RA 16 headstage and amplifier, and 4 RA 16 Base Stations for
analog input, also using OpenEx.
r '.t JhiS laboratory is used for electrophysiological recordings using dichotic stimuluation. It includes an
~.A.C. aou e-walled sound-insulated chamber used for dichotic electro physiological recording experiments. The
lab is armed with a broad array of specialized peripheral devices for delivering digital auditory signals, including a
two-channel DSS. In addition the lab has all of the electrophysiological amplifiers, oscilloscopes, B & K
microphones, earphones, microscopes, electrode pullers, etc. to carry out the proposed work. This includes
Dagan 2400 extracellular and Dagan 8100 intracellular amplifiers, Tektronix 2430 and 2220 digital storage
oscilloscopes, and a locally built peak detector for timing spikes to the peak of the action potential. This facility can
handle all of the acoustic calibrations, generation of stimuli, and data collection, storage, and analysis, to complete
a wide range of single-neuron studies.
\ ';k ~hiS laboratory is used for electrophysiological experiments using free field stimulation. It contains a
sII,alle, (7' 8') lAC. sound-insulated booth, the inside walls of which have been lined with 4" Sonex foam to form
an anechoic chamber. A semicircle of 13 matched speakers (Monel MDJ-20 or Radio Shack midrange tweeters)
spaced at 1S-degree increments are mounted along the horizontal meridian at 9S cm radius. The speakers are
selected by a 16 channel, relay speaker selector that uses input from an 8-bit parallel I/O. Two independent Crown
amplifiers will drive the two speakers. This system is presently connected to a pair of DSSs and a V AX station
shared with another lab. A full complement of electrophysiological recording equipment (BAK pre-amps, AC
amplifiers, window discriminator, oscilloscopes, and audio monitors) and Trent-Wells stepping motor microdrive
are available for free-field physiological work. We are proposing to use this smaller sound-proof room for training
of animals by moving the present search coil system into this room.
Equipment Page 9
2011-04-22 000018
Principallnvestigator/Program Director (last, first, middle): YIN, TOM, C T
~~~~I~~~~~~t!~Sf:~i~i~\CCUPYillg SOl I Ie 900 itt.

of space adjaCent
This facility, which serves the entire Medical School, has a full
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complemento~tesilng
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and measurement
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equipment. Schematic design and layout of customized electronic equipment is greatly facilitated by CAD
software. The ShO. P is equipped with machine tools for fabrication, including benders, drill press, mil~:g m:~chlne
*
and lathe. The staff includes two full time engineers, who provide technical advice and support. Mrt. ~.~
jas been serving the Department for over 20 years and knows well the lab instrumen;;t.;s"a"'nrr---
Instrumentation needs of the P.1.
Computing: . re linked via a high-

speed Local or ,w IC IS connec e 0 e campus ac one, an to the Internet. The
building has undergone a major network upgrade within the past year, with all wiring upgraded from Cat3 to
Cat6. This has increased network speed by a factor of 10 (from 10 Mbps to 100 Mbps) to all computers, and to
'1000 Mbps in some cases. A new firewall has been added to isolate and protect the Physiology network.
Within the Physiology LAN we use TCP/lP, AppleTalk and NetBEUI as the network protocols, with the latter
two being gradually phased out in favor of TCP/IP. There are also plans to migrate from IPv4 to IPv6. A
building-wide wireless network now provides additional options for laptops and other devices. The Medical
School provides funds for connecting all computers and workstations to the main switches, as well as to the
rest of the campus. The PC's)-lsed for exper,:ental control (described above) and those used for data analysis
are all part of this network. Mr.[ ~ ~>.J.Js responsible for monitoring, upgrading and maintaining the '
network.
Campus-wide computing network: The University of Wisconsin-Madison places a major emphasis on the
use of computer networks for both education and research. Over the last 3 years, a major network initiative
(dubbed "21st Century Network") has resulted in a greatly improved campus backbone. All offices and labs
have been rewired with Cat6 cabling (capable of 1000 Mbps). All switches and routers have been upgraded,
and the campus backbone now supports 10 Gbps throughput. The Division of Information Technology (DolT)
provides coordination as well as funds for the shared portions of this campuswide resource. The DolT Network
Operations Center is staffed 24-hours to monitor and fix any problems affecting the campus backbone and
connectivity to the Internet. The new higher-speed network supports Digital Video (DATN) and Voice (VoIP)
communications. The University of Wisconsin is a participant in the Internet2 consortium, a group of more than
200 universities working with industry and government to develop and deploy advanced network applications
and technologies.
Neurohistology: Neurohistological service is provided by the histology laboratory of the Department of

Neurophysiology. This lab is fully equipped to carry out a wide variety of procedures, from standard Nissl
preparations to more demanding immunocytochemistry.
Auditory group at the University of Wisconsin: Research in the auditory system at many levels has had a long
and distinguished history in the Department of Neurophysiology, which merged with the Department of Physiology
in 1998. It began over 38 years ago under the direction of Drs. Jerzy E. Rose and Clinton E. Woolsey and has
continued and expanded considerably over the last 10-20 years. The primary mode of interaction within this group
is a year-round seminar series which the P.1. established 25 years ago and continues in the form of a "Hearing
and Donuts" meeting every Friday morning. Its major aim is to provide critique of work in progress and feedback to
investigators early in the development of an idea or project. All investigators, including those within the
department and elsewhere on campus, with interest in the auditory system attend regularly. Talks are scheduled
in turn and attendance is about 2 and a half dozen donuts worth so that a talk is given about once a year. A
considerable number of talks are also iven b visitin s eakers. The followin facul ..
artici ate in this series:
here are few other places In e war were suc a arge an velse w"""unl 0 auditory
Ie on a weekly basis to discuss issues of common interest, which include ion channel biophysics,
Equipment Page 10
~ ~'ll)l~ tlcJ ['\0+ -tumlLJ, ~ t:ylo.J.

2011-04-22 000019
hair cell transduction, coding in the central auditory system, modeling of the auditory periphery and eNS, and
human psychophysics. Thus, Hearing and Donuts provides several crucial services: a forum for everyone
involved in auditory research to become familiar with work done in each lab, an avenue for students to present
seminars on a regular basis before a friendly but critical audience, and an opportunity for outside speakers to
address an unusually large and active auditory community. This rich environment of interest in the auditory
system provides an invaluable resource for this grant.
In addition the P.1. has close ties with other neuroscientists at uw-~adison
stimulating environment. In particular, the research interests of Dr.{?f:
10 provide a rich and
J.vith whom the P.1. taught
medical students for over 20 years, on the visual system and the superior colliculus dovetail nicely with our
interests.
Equipment Page 11
2011-04-22 000020
Principallnvestigalor/Program Director (Last, first, middle): YIN, TOM, C T
RESEARCH & RELATED Senior/Key Person Profile (Expanded)
PROFILE ~ Project Director/Prlnclpallnvestigator

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• last Name: IYIN I Suffix: I I
PositionfTille: IPROFESSOR
I Department: IPHYSIOLOGY I
Organization Name:IThe Board of Regents of the UW System I DiViSion:IMedicine and Public Health I
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* City: IMADISON I County: IDane I
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* Phone Number:!6082620368
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** ... Key personnel Page 12
Tracking Number:GRANTl0194930 FundIng Opportunity Number:PA-07-070 Received Date:2009-03-04TlS:42:32-04:00
2011-04-22 000021
PrincipallnvestigatorlProgram Director (Last, first, middle): YIN, TOM, C T
RESEARCH & RELATED Senior/Key Person Profile (Expanded)
PROFILE. Senior/Key Person 2
Prefix:r • Firsl Name=[ \:.::r~ I Middle Name:! I

• Last Name: n -sF T I SUffiX:! I
Positionrrme: r\ r I Department: fj :3 I
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ADDITIONAL SENIOR/KEY PERSON PROFILE(S) Add Atla,clJm~nt I,Delete'Attachillsnl-, :';yIeHvAltachmenl: I

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OMB Number: 4040-0001

Expiralion Dale: 04/30/2008
Key Personnel Page 13
Tracking Number:GRANTl0194930 Funding Opportunity Number:PA-07·070 Received Date:2009-03-04T15:42:32-04:00
2011-04-22 000022
Principallnvestigator/Program Director (Last, First, Middle): Yin, Tom C.T.
BIOGRAPHICAL SKETCH
Provide the fol/owing Information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME POSITION TITLE

Tom C.T. Yin Professor of Physiology
-t=iifOC'1~Mit:MiCoiNNsSijuSisEEFRiiNwAii:MU;E""--",,--------1 Chair, Neuroscience Training Program
EOUCATIONfTRAINING (Begin with baccalaureate or other Initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION DEGREE YEAR(s) FIELD OF STUDY

lif applicable)
Princeton University B.S.E. 1966 Electrical Engineering
University of Michigan Ph.D. 1973 Elect. & Compo Engr.
State University of New York at Buffalo Postdoc. 1974 Biophysics & Physiology
Johns Hopkins University Postdoc. 1974-77 Physiology
A. Positions and Honors:

1977-1997 Assistant Professor to Professor, Dept. of Neurophysiology, Univ. of Wisconsin, Madison.
1997-pres Professor of Physiology (by merger), Univ. of Wisconsin, Madison.
2006-pres Chair, Neuroscience Training Program, UW-Madison
2004-pres P.I., Training program in clinical neuroengineering, UW-Madison
1984-1988 Member of N.I.H. Biopsychology (BPO) Study Section
1992-1996 Member of N.I.H. Hearing Research (HAR) Study Section
1991 Visiting faculty, Vision, Touch and Hearing Research Centre, Univ. of Queensland, Australia.
2003 Chancellor's Distinguished Teaching Award, Univ. of Wisconsin-Madison.
2004- pres Assoc. for Research in Otolaryngology Mid-Winter Meeting Program Committee
2005- 2007 Associate editor, Journal of Association for Research in Otolaryngology
2003- pres Editorial board, Journal of Neurophysiology
2003- pres Editorial board, Hearing Research
2005- pres. Various NIH study sections ZDC1, ZDA1, ZRG1, ZDE1 NB89 (chair)
B. Selected Publications:
Yin, T.C.T. and Williams, W.J. Dynamic response and transfer characteristics of joint neurons in
somatosensory thalamus of the cat. J. Neurophysio/. 39: 582-600, 1976.
Allen, G.I., Gilbert, P.F.C., Marini, R., Schultz, W., and Yin, T.C.T. Integration of cerebral and peripheral
inputs by interpositus neurons in monkey. EXp. Brain Res. 27: 81-99,1977.
Lynch, J.C., Mountcastle, V.B., Talbot, W.H., and Yin, T.C.T. Parietal lobe mechanisms for directed visual
attention. J. Neurophysio/. 40: 362-389, 1977.
Yin, T.C.T. and Mountcastle, V.B. Visual input to the visuomotor mechanisms of the monkey's parietal lobe.
Science 197: 1381-1383,1977.
Allen, G.I., Gilbert, P.F.C., and Yin, T.C.T. Convergence of cerebral inputs onto dentate neurons in monkey.
Exp. Brain Res. 32: 151-170, 1978.
Kuwada, S., Yin, T.C.T., and Wickesberg, R.E. Response of cat inferior coiliculus neurons to binaural beat
stimuli: possible mechanisms for sound localization. Science 206: 586-588, 1979.
Hedreen, J. and Yin, T.C.T. Homotopic and heterotopic callosal afferents of caudal inferior parietal lobule in
Macaca mulatta. J. Comp. Neuro/. 197: 605-621,1981.
Kuwada, S. and Yin, T.C.T. Binaural interaction in low-frequency neurons in inferior coiliculus of the cat. I.
Effects of long interaural delays, intensity, and repetition rate on interaural delay function. J.
Neurophysio/. 50: 981-999,1983.
Yin, T.C.T. and Kuwada, S. Binaural interaction in low-frequency neurons in inferior colliculus of the cat. II.
Effects of changing rate and direction of interaural phase. J. Neurophysio/. 50: 1000-1019,1983.
PHS 398/2590 (Rev. 11107) Page_ Biographical Sketch Format Page

Biosketches Page 14
2011-04-22 000023
Principal Investigator/Program Director (last First, Middle): Yin! Tom C.T.

Yin, T.C.T. and Kuwada, S. Binaural interaction in low-frequency neurons in inferior colliculus of the cat. III.
Effects of changing frequency. J. Neurophysiol. 50: 1020-1042, 1983.
Kuwada, S., Yin, T.C.T., Syka, J., Buunen, T.J.F., and Wickesberg; R.E. Binaural interaction in
low-frequency neurons in inferior colliculus of the cat. IV. Comparison of monaural and binaural response
areas. J. Neurophysiol. 51: 1306-1325,1984.
Yin, T.C.T., Kuwada, S., and Sujaku, Y. Interaural time sensitivity of high frequency neurons in the inferior
colliculus. J. Acoust. Soc. Amer. 76: 1401-1410, 1984.
Hirsch, JA, Chan, J.C.K., and Yin, T.C.T. Responses of neurons in the cat's superior colliculus to acoustic
stimuli. I. Monaural and binaural response properties. J. Neurophysiol. 53: 726-745, 1985.
Yin, T.C.T., Hirsch, JA, and Chan, J.CK Responses of neurons in the cat's superior colliculus to acoustic
stimuli. II. A model of interaural intensity sensitivity. J. Neurophysiol. 53: 746-758,1985.
Yin, T.C.T., Chan, J.C.K., and Irvine, D.R.F. Effects of interaural time delays of noise stimuli on
low-frequency cells in the cat's inferior colliculus. I. Responses to wide-band noise. J. Neurophysiol. 55:
280-300, 1986.
Chan, J.C.K., Yin, T.C.T., and Musicant, A.D. Effects of interaural time delays of noise stimuli on
low-frequency cells in the cat's inferior colliculus. II. Responses to band-pass noise. J. Neurophysiol.
58: 543-561,1987.
Yin, T.C.T., Chan, J.C.K. and Carney, L.H. Effects of interaural time delays of noise stimuli on low-frequency
cells in the cat's inferior colliculus. III. Evidence for cross-correlation. J. Neurophysiol. 58: 562-583,
1987.
Carney, L.H. and Yin, T.C.T. Temporal coding of resonances by low-frequency auditory nerve fibers: single
fiber responses and a population model. J. Neurophyslol. 60: 1653-1677, 1988.
Carney, L.H. and Yin, T.C.T. Responses of low-frequency cells in the inferior colliculus to interaural time
differences of clicks: excitatory and inhibitory components. J. Neurophysiol. 62: 141-161, 1989.
Yin, T.C.T. and Chan, J.C.K. Interaural time sensitivity in medial superior olive of cal. J. Neurophysiol. 64:
465-488, 1990.
Oliver, D.L., Kuwada, S., Yin, T.C.T., Haberly, L.B., and Henkel, C.K. Dendritic and axonal morphology of
single neurons in the inferior colliculus of the cat. J. Comp. Neurol. 303: 75-100,1991.
Smith, P.H., Joris, P.X., Carney, L.H. and Yin, T.C.T. Projections of physiologically-characterized globular
bushy cell axons from the cochlear nucleus of the cat. J. Comp. Neurol. 304: 387-407,1991.
Joris, P.X. and Yin, T.C.T. Responses to amplitude-modulated tones in the auditory nerve of the cat. J.
Acoust. Soc. Amer. 91: 215-232, 1992.
Yin, T.C.T. and Greenwood, M. Visual response properties of neurons in the middle and lateral suprasylvian
cortices of the behaving cat. Exp. Brain Res. 88: 1-14,1992.
Yin, T.C.T. and Greenwood, M. Visuomotor interactions in the middle and lateral suprasylvian cortices of the
behaving cat. Exp. Brain Res. 88: 15-32, 1992.
Smith, P.H., Joris, P.X., and Yin, T.C.T. Projections of physiologically characterized spherical bushy cell
axons from the cochlear nucleus of the cat: evidence for delay lines to the medial superior olive. J.
Comp. Neurol. 331: 245-260,1993.
Joris, P.X., Carney, L.H., Smith, P.H. and Yin, T.C.T. Enhancement of neural synchronization in the
anteroventral cochlear nucleus. I. Responses to tones at the characteristic frequency. J. Neurophysiol.
71: 1022-1036, 1994.
Joris, P.X., Smith, P.H., and Yin, T.C.T. Enhancement of neural synchronization in the anteroventral
cochlear nucleus. II. Responses to tones in the tuning curve tail. J. Neurophysiol. 71: 1037-1051,1994.
Yin, T.C.T. Physiological correlates of the precedence effect and summing localization in the inferior
colliculus of the cat. J. Neurosci. 14: 5170-5186,1994.
Joris, P.X. and Yin, T.C.T. Envelope coding In the lateral superior olive. I. Sensitivity to interaural time
differences. J. Neurophysiol. 73: 1043-1062, 1995.
Populin, L. and Yin, T.C.T. Topographical organization of the motoneuron pools that innervate the muscles
of the pinna of the cat. J. Comp. Neurol. 363: 600-614, 1995.
Kuwada, S., Batra, R., Yin, T.C.T., Oliver, D.L., Haberly, L.B., and Stanford, T.R. Intracellular recordings in
response to monaural and binaural stimulation of neurons in the inferior colliculus of the cat. J. Neurosci.
17: 7565-7581,1997.
PHS 398/2590 (Rev. 11107) Continuation Format Page

Biosketches Page 15
2011-04-22 000024
Principal Investigator/Program Director (Last, First, Middle}: Yin, Tom C.T.
Joris, P.X. and Yin, Tom C.T. Envelope coding in the lateral superior olive. III. Comparison with afferent
pathways. J. Neurophyslo/. 79: 253-269, 1998. PMID: 9425196
Populin, L.C. and Yin, T.C.T. Behavioral studies of sound localization in the behaving cat. J. Neurosci. 18:
2147-2160,1998.
Populin, L.C. and Yin, T.C.T. Pinna movements of the cat during sound localization. J. Neurosci. 18:
4233-4243, 1998.
Smith, P.H., Joris, P.X. and Yin, T.C.T. Anatomy and physiology of principal cells of the cat medial nucleus
of the trapezoid body (MNTB). J. Neurophysio/. 79: 3127-3142,1998.
Litovsky, R.Y. and Yin, T.C.T. Physiological studies of the precedence effect in the inferior colliculus of the
cat: I. Correlates of psychophysics. J. Neurophysio/. 80: 1285-1301, 1998.
Litovsky, R.Y. and Yin, T.C.T. Physiological studies of the precedence effect in the inferior colliculus of the
cat: II. Neural mechanisms. J. Neurophysio/. 80: 1302-1316, 1998.
Joris, P.X., Smith, P.H. and Yin, T.C.T. Coincidence detection in the auditory system: 50 years after
Jeffress. Neuron 21: 1235-1238, 1998.
Delgutte, B., Joris, P.X., Litovsky, R.Y. and Yin, T.C.T. Responses to virtual-space stimuli in the cat inferior
colliculus. I. Types of sensitivity and binaural interactions J. Neurophyslo/. 81: 2833-2851, 1999.
Populin, L.C. and Yin, T.C.T. Kinematics of eye movements of cats to broadband acoustic targets. J.
Neurophysio/. 82: 955-962, 1999.
Tollin, D.J. and Yin, T.C.T. The coding of spatial location by single units in the lateral superior olive of the
cat. I. Spatial receptive fields in azimuth. J. Neurosci. 22: 1454-1467,2002.
Tollin, D.J. and Yin, T.C.T. The coding of spatial location by single units in the lateral superior olive of the
cat. II. The determinants of spatial receptive fields in azimuth. J. Neurosci. 22: 1468-1479,2002.
Populin, L.C. and Yin, T.C.T. Bimodal interactions in the superior colliculus of the behaving cat. J.
Neurosci. 22: 2826-2834, 2002.
Tollin, D.J. and Yin, T.C.T. Spectral cues explain illusory elevation effects with stereo sounds in cats. J.
Neurophysio/. 90: 525-530, 2003. (subject of an Editorial Focus article)
Tollin, D.J. and Yin, T.C.T. Psychophysical investigation of an auditory spatial illusion in cats: The
precedence effect. J. Neurophysio/. 90: 2149-2162, 2003. PMClD: PMC2504554
Batra, R. and Yin, T.C.T. Cross-correlation by neurons in the medial superior olive: a re-examination. J.
Assoc. Research Otolaryngo/. 5: 238-252, 2004. PMC2504554
Dent, M.L., Tollin, D.J., and Yin, T.C.T. Cats exhibit the Franssen effect illusion. J. Acoust. Soc. Amer.
116: 3070-3074, 2004.
Populin, L.C., Tollin, D.J., and Yin, T.C.T. Effect of eye position on saccades and neuronal responses to
acoustic stimuli in the superior colliculus of the behaving cat. J Neurophysio/. 92: 2151-2167, 2004.
Tollin, D.J., Populin, L.C., and Yin, T.C.T. Neural correlates of the precedence effect in the inferior colliculus
of behaving cats. J. Neurophysio/. 92: 3286-3297, 2004.
Tollin, D.J., Populin, L.C., Moore, J., Ruhland, J.L., and Yin, T.C.T. Sound localization performance in the
cat: the effect of restraining the head. J. Neurophyslo/. 93: 1223-1234, 2005. (subject of Editorial
Focus).
Tollin, D.J., Populin, L.C., Moore, J., Ruhland, J.L., and Yin, T.C.T. Response to Letter to Editor ("Heffner,
H.E. and Heffner, R.S. "The sound-localization ability of cats" J. Neurophysiol. 94: 3653-3655, 2005).
Dent, M.L., Tollin, D.J. and Yin, T.C.T. Psychophysical and physiological studies of the precedence effect in
cats. Acta Acustica 91: 463-470, 2005.
Tollin, D.J. and Yin, T.C.T. Interaural phase and level difference sensitivity in low-frequency neurons in the
lateral superior olive. J. Neurosci. 25: 10648-10657,2005. PMCID: PMC1449742
Joris, P.X. and Yin, T.C.T. A matter of time: internal delays in binaural processing. Trends in Neurosci. 30:
70-78, 2007.
Moore, J.M., Tollin, D.J. and Yin, T.C.T. Can measures of sound localization acuity be related to the
precision of absolute location estimates? Hear. Res. 238: 94-109, 2008. PMCID: PMC2494532
Tollin, D.J., Ruhland, J.L., and Yin, T.C.T. The vestibulo-auricular reflex. J. Neurophysio/. 101: 1258-1266,
2009. PMC journal- in process.
PHS 398/2590 (Rov. 11/07) Page_ Continuation Format Page

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2011-04-22 000025
Principallnvestigator/Program Director (Last, First, Middle): Yin, Tom C.T.
Recent Book Chapters

Yin, T.C.T. Neural mechanisms of encoding binaural localization cues in the auditory brainstem. In Integrative
Functions in the Mammalian Auditory Pathway, D. Oertel, A.N. Popper, and R.R. Fay, Eds. Springer-
Verlag, Springer Handbook of Auditory Research, pp. 99-159, 2002.
Yin, T.C.T. and May, B.J. Acoustic behavior and midbrain function. In The Inferior Colliculus, J.A. Winer,
C.E. Schreiner, A.N. Popper and R.R. Fay, Eds. Springer-Verlag, Springer Handbook of Auditory
Research, pp. 426-458, 2005.
Tollin, D.J. and Yin, T.C.T. Sound localization: neural mechanisms. In Encyclopedia of Neuroscience,
Volume 9 Larry Squire, (Ed.), Oxford: Academic Press, pp. 137-144,2009.
Yin, T.C.T. Audition. In Neuroscience in Medicine, 3'd edition, P. Michael Conn, Ed. Totowa, N.J.:
Hum"n" Drocc nn fi7fi-fiRq 700R
(in press).
(in press)
C. Research ongoing or completed during the last three years:
Ongoing
R01 DC07177-3 NIH/NIDCD Role: P.I. 1211/04 to 11/30109
"Sound localization and selective auditory attention"
The overall objective is to use the behavioral preparation that we have developed over the past 10 years to
continue a series of psychophysical and physiological studies.
T32 GM007507-29 NIH/NIGMS Role: P.I. 7/01/78 to 6/30/13
"Neuroscience Training Program"
The goal is to train predoctoral students in integrative neurobiology who will be among the leaders in the next
generation of neuroscientists
T90 DK070079-3 NIH/NIDDK Role: P.I. 1011/04 to 9130109
"Training program in clinical neuroengineering"
The goal of this project is to train predoctoral candidates in interdisciplinary approaches that span
neuroscience and biomedical engineering and are relevant to clinical problems in neurology and
neurosur e .
'PY'lw. +t-S "P Cy+ ole: co-PI 9/1/07 to 4/1/09
easlbility stu les uSing latera coc ear implants in cats (R. Litovsky, P.I.)
The goal is to collect pilot data on the behavioral performance of cats who are trained in a sound localization
task, deafened with ototoxic drugs and then given bilateral cochlear implants.
Completed
R01 DC02840-11 NIH/NIDCD Role: P.I. 3/01/96 to 2/28/06
"Behavioral and physiological studies of soul]d localization"
The overall goal of this project is to integrate behavioral and neurophysiological methods to study sound
localization in cats using psychophysical studies of sound localization in the awake cat, to study the
movements of the external ears in cats that are actively localizing sounds, and to initiate physiological
recordings in the superior and inferior colliculus in these animals.
PHS 398/2590 (Rev. 11/07) Page_ Continuation Format Page

Biosketches Page 17
2011-04-22 000026
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2011-04-22 000027
Principallnvestigator/Program Director {Last. first. middle}: YIN. TOM. C T
PHS 398 Cover Page Supplement
1. Project Director / Principal Investigator (PO/PI)
Prefix: lor. I I< First Name: ITOM I

Middle Name: Ie T I
I< Last Name: IYIN I
Suffix:
I I
I< New Investigator? ~No DVes
Degrees: Ipho > I I I I I
2. Human Subjects
.
Clinical Trial?
~No DVes
. . Agency~Defined Phase III Clinical Trial? oNo DVes
3. Applicant Organization Contact
Person to be contacted on matters involving this application
Prefix:
I . . First Name: L I
~
Middle Name: I
Last Name: I I
Suffix: I
Phone Number: I\ ~ J I Fax Number: 11 j I
Email: II .. 'i'- J I
'Title:[\' ¥: ) I
.
* Street1: ' l }\/ 1 t I
Street2:
City:
'u,.. _::l J
I<
I\.~ I
County:
LL.,1 I
... State:
WI: (~ I
Province:
I
. . Country:
c:-~ I I I< Zip I Postal Code: I· L.~
I
t '-'(\~l~' ~~ Cor.+o.ct ~OI""""~ {c.,.,\\a'oClr~.o~
Clinical Trial & HESC Page 25
Tracking Number:GRANTI0194930 Funding Opportunity Number:PA~07-070 Received Date:2009-03-04TlS:42:32-04:00
2011-04-22 000028
PrincipallnvestigatorlProgram Director (Last, first, middle): YIN. TOM, C T
PHS 398 Cover Page Supplement
4. Human Embryonic Stem Cells
* Does the proposed project involve human embryonic stem cells? [8J No DYas
If the proposed project involves human embryonic stem eel/s.list below the registralion number of the
specific celiline{s) from the following list: hUp:f1stemcells.nih.gov/registrylindex.asp. Or. if a specific
stem cell line cannot be referenced at this time, please check the box indicating that one from the
registry will be used:
Cell Line(s): o Specific stem cell line cannot be referenced at this time. One from the registry will be used.
Clinical Trial & HESC Page 26
Tracking Number:GRANTl0194930 Funding Opportunity Number:PA·07·070 Received Date:2009·03 ·04Tl5:42:32·04:00
2011-04-22 000029
PHS 398 Modular Budget, Periods 1 and 2

OMB Number: 0925·0001
Budget Period: 1
Reset Entries I Slart Dale:112/01/2009
1
End Date:I11130/2010
I
A. Direct Costs • Funds Requesled--'ll
,. Direct Cost less Consortium F&A I 250,000.00
Consortium F&A I I
,. Total Direct Costs I 250,000.001
B. Indirect Costs Indirect Cost Indirect Cost

Indirect Cost Type Rale (%) Base ($) • Funds Requesled ($)
1.IMTDC 0o_campus I' 48.51! 242.000.0011 117,370.001
2·1 ICJI I I
3·1 ICJI I I
4'1 I' II II I
Cognizant Agency (Agency Name, POC Name and Phone Number) DHHS, Henry Williams, Dallas, 214-767-3261
Indirect Cost Rate Agreement Date 103131/2008

I Total Indirect Costs I 117,370.001
C. Total Direct and Indirect Costs (A + B) Funds Requested ($) I 367,370.001
Budget Period: 2
Reset Entries I Slart Dale: 112/01/2010
I End Dale: 11113012011
I
A. Direct Costs • Funds Renuesled lSI
,. Direct Cost less Consortium F&A I 250,000.00
Consortium F&A I I
,. Total Direct Costs I 250,000.001
B. Indirect Costs
Indirect Cost Indirect Cost
1. IMTDC 0o_campus
I~I 242,000,0011 117,370. 001
2. I' II II
I
3. II II I I
I
4. I
I ICJI
I
Indirect Cost Rate Agreement Date 103/31/2008

I Totallndirect Costs I 117,370.0°1
C. Total Direct and Indirect Costs (A + B) Funds Requesled ($) I 367,370.001
Modular Budget Page 27
Tracking Number:GRANTl 0194930 Funding Opportunity NUmber:PA·07·070 Received Date:2009·03·04TJ 5:42:32·04:00
2011-04-22 000030
PHS 398 Modular Budget, Periods 3 and 4
Budget Period: 3
Reset Entries I Start Date: 112/01/2011
I End Dale: 111130/2012
I
A. Direct Costs • Funds Requesled ($)
* Direct Cost less Consortium F&A I 250,000.00
I,
Consortium F&A I
* Total Direct Costs I 250 t ooo.ool
Indirect Cost Type Rale (%) Base ($) * Funds Requested ($)
1.IMTDC On_campus
II 48.511 242.000.0011 117,370.001
II ,
2·1
I' ,
3'1 I " II
4.
"
Cognizant Agency (Agency Name, POC Name and Phone Number) OHHS, Henry Williams, Dallas, 214-767-3261
Indirect Cost Rate Agreement Date 103/31/2008

I Total Indirect Costs
I 117,370.0°1
Budget Period: 4
Reset Entiies I Start Date: 112101/2012
I End Date: 111/30/2013
I
A. Direct Costs * Funds Requested ($)
I,
Consortium FAA I
* Total Direct Costs I 250,000.001
B. Indirect Costs
Indirect Cost Indirect Cost
1.
2.
IMTDC On_campus
I 48·'11 242.000.0011 117,370·°°1
,
II
1 I' ,
3.
1 ILJI" II
4.
Indirect Cost Rate Agreement Date!o3/31/2008

I Tolallndirect Costs I 117,3 70.001
C. Total Direct and indirect Costs (A + B) Funds Requesled ($)

I 367,370.001
Modular Budget Page 26
Tracking Number:GRANTlO194930 Funding Opportunity Numbcr:PA~07~070 Receh'cd Date:2oo9·03·04Tl 5:42:32·04:00

2011-04-22 000031
PHS 398 Modular Budget, Periods 5 and Cumulative
Budget Period: 5
Reset Entries I Start Date: 112/01/2013
I End Date: 11113012014
I
A. Direct Costs • Funds Requested ($)
I
Consortium F&A I I
* Total Direct Costs I 250,000.001

Indirect Cost Type Rate ('Yo) Base ($) * Funds Requested ($)
1. IMTDC On campus
II 4 •• 511 242,000.0011 117,370.001
21 II II I I
3 I II II I I
4·1 II II I I
Indirect Cost Rate Agreement oatel03/31/2008

I Total Indirect Costs
I 117,370.001
Cumulative Budget Information

1 I
1. Total Costs, Entire Project Period
*Section A, Total Direct Cost less Consortium F&A for Entire Project Period $1 1,250,000.0°1
Section A, Total Consortium F&A for Entire Project Period $1 I

*Section A, Total Direct Costs for Entire Project Period $1 1,250,000.001
*Section B, Total Indirect Costs for Entire Project Period $/ 586,850.001
*Section C, Total Direct and Indirect Costs (A+B) for Entire Project Period $1 1,836,850. 001
2. Budget Justifications
Personnel JUstification IPerSOnnelJUstificationlO048841 Add Attachment
I Delete- Al!a-c.hment I VieY/Atlac~mlinI -I
Consortium Justification
I I Add AUachment
I C' C
Delete AUacpmefll VieWAuaChm~n(--1
Additional Narrative Justificationl
I Add AUachment
I Delete Attachment Vie\~:AU2chn1~nt --I
Modular Budget . Page 29
Tracking Number:GRANTl 0194930 Funding Opportunity Number:PA -07-070 R«:eh'ed Date:2009- 03- 04T 15:42:32-04:00
2011-04-22 000032
PERSONNEL
Tom C.T. Yin, Ph.D., Principal Investigator, p calendar months, is responsible for the scientific direction
of the projects and will participate in all phases r' it, including: designing the experiments, collecting and
analyzing the data, and writing up the results.
t tl( :oJ Research Specialist, 0 calendar months, has the primary responsibility for
overseeing the animal husbandry and behavioral training of the cats. She is indispensable for these
experiments. She has worked in the lab for almost 10 years, and also has responsibility for ordering supplies,
preparation of sterile packs for the surgeries, training and supervising the many undergraduate workers in the
lab, and general welfare of the animals. She also participates actively in experimental design, data analysis
and writing up the results for publication
\ iK ::\ Senior Info. Processing Consultant (progrl)mmer), p calendar months, does the
programming speCific to our behavioral training experiment. She !las been with the department for over 20
years. She has written all of the behavioral training computer package, and she has primary responsibility for
modifications and maintenance of this complex suite of real-time programs.
'(===~¥~i==}:J' Research Assistant, \Jpalendar months, is a graduate student in the---o'kC;--~

'C ~ ) and is working C _ ;4. ~ ; in the lab.
He will be helping us with the experiments involving plugging of

the semicircular canals. He has considerable experience with that procedure in human patients and
nonhuman primates.
*
f:-:=:::;==::-:::-::===-:-:::=-::-:::-::::-::;-=::-:-:==--=::-;:::::-;=-=-:;;::~:::.=-~_,..,.
our experiments to selectively cool the auditory cortex and/or the midbrain.
J
,~__.-,!r:..-:::,:=:;l. He will assist in
1
,J: 'r\~1 o.~, QVn.~ C-'>I,~d- 40f~ 1~ ~

~\lobor~ ~~.llJ.,.
Personnel JUstification Page 30
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PrincipallnvesligatorlProgram Director (last, first, middle): YIN, TOM, C T
Close For.m 1 Print Page I. About 1
OMS Number. 0925-0001
PHS 398 Research Plan

1. Application Type:
From SF 424 (R&R) Cover Page and PHS398 Checklist. The responses provided on these pages, regarding the type of application being submitted,
are repeated for your reference, as you aUach the appropriate sections of the research plan.
*Type of Application:
o New D Resubmission IZl Renewal o Continuation o Revision

2. Research Plan Attachments:
Please aUach applicable sections of the research plan, below.
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4. Preliminary Studies / Progress Report IprOgreSSRepOrtl004 9009']5 ,Pdl Add-Attachment Delel~--Alia,Chnle:nfl Vlew,/\Uachment I
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9. Inclusion of Women and Minorities I I Add Allachment I Qel~te. Attac.hmEmt I Yi~w-'AUachinent I
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Defete /Illachrnent
14. Multiple PI Leadership Plan I I Add Allachmeritl Delete ~llachl'1.nt I ,ViEiy·(Atla7c,hm_e~i I
15. Consortium/Contractual Arrangements I I Ad<l Allachmeni I .Del~I~;Att~~chmen{.:1 ~ ·-Vlew'Attachment:, I
16. Letters of Support
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list of Research Plan Attachments Page 31
Tracking Number:GRANTI0194930 Funding Opportunity Number:PA-07-070 Received Date:2009-03-04T15:42:32·04:00
2011-04-22 000034
A. SPECIFIC AIMS
The overall objective of this proposal is to study the neural mechanisms of binaural hearing, particularly
as they relate to spatial processing. We propose to use the behavioral preparation developed in our lab
over the past decade to continue a series of psychophysical and physiological studies aimed at elucidating
the role of the auditory midbrain (inferior and superior colliculus) and auditory cortex in localization and
investigating the role of the mobility of the external ears, or pinnae, of the cat for sound localization.
Specific Aim I. This specific aim tests the hypothesis that the neural correlate of spatial orientation to
sounds by the head, eyes and ears is at a .subcorticallevel involving the midbrain structures, the inferior anc
superior col/iculus. Aim la will examine the effects of inactivating two auditory cortical areas on orientation
of the eyes, head and ears. While cortical cooling has been shown to have dramatic effects on sound
localization, the behavioral response required the cats to orient and walk to the speakers. We hypothesize
~!h~' - % ~_" - ]
I 1m WI examine tee ect 0
_~jt' ssumlng a we get the expected result in aim la, tkh:r:is:-a::1ir::m:-tr.:e~sT.ts:-t=e-=y:::p:::o:n::'e9s~i=-n:-:a:-rt"l1t"'e::----
'*" -
Aim Ic will examine the effect 0
-~
his aim will test t a
~~~~~------------------------~
Specific aim II. This specific aim tests the hypothesis that the mobility of the external ears in the cat is
designed to provide a stable acoustic world despite rapid movements of the head. Aim lIa will determine if
the vestibulo-auricular reflex (VAR), which was discovered during the previous grant period, Is triggered by
the vestibular system byexaminln the effects of deactivation of the vestibular system on the reflex.
-Assumln that we get the ypothesized result that th
:Jf. 1m lib will stud the effect of '
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~~_~lAim IIc will to er test the hypothesis tha£--_ _ _ _ _---'-::s:.._ _ _ _ _ _ _ _ _ __
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Specific aim III This aim views the pinna as a model system for studying motor control much like the
oculomotor system has served as the best-understood motor control system. Aim ilia will
examine e e
owe
~--"t1nI""m;;--nr.c:--;w=l1 directl
Specific Aims -Page 32
2011-04-22 000035
Principallnvestigator/Program Director (Lasl, first, middle): YIN, TOM. C T
B. BACKGROUND AND SIGNIFICANCE

Introduction
The ability to localize the source of a sound is an important function of the auditory system. It is of obvious
value for both prey and predator to quickly and accurately identify the location of a sound source.
Consequently, the mechanisms underlying sound localization have been of great interest to psychophysicists,
anatomists and physiologists studying the auditory system. Our lab has been studying the physiological and
anatomical mechanisms by which sound localization cues are encoded in the central auditory system for the
last 30 years. Arguably, we understand more about the central processing of sound localization cues than
that of any other auditory attribute (see Irvine, 1986; Yin, 2002), though recent work in pitch and source
identification are promising (Bendor and Wang, 200;;; Fritz et al., 2005; 2007). The overall goal of this
research program is to combine behavioral and physiological methods to study sound localization in cats.
An important objective is to record the activity of neurons in the auditory system that are important for sound
localization while the cat is actively engaged in a localization task. We believe that careful psychophysics is
a key ingredient to success in such a combined project. In our previous studies we have developed a
powerful behavioral sound localization preparation in which cats are trained to look at sound sources, either
with their heads restrained ("fixed") or unrestrained ("free"). In the present renewal we propose to extend
our studies of the neural mechanisms of sound localization behavior to explore the role of the auditory
cortex and auditory midbrain in orienting to sound as well as further studies of the external ear and the VAR.
We believe that the combined behavioral and physiological recording experiments are a Significant
short-coming in the auditory literature. Indeed it is remarkable how much progress has been made in
studies of awake, behaving animals in the visual and somatosensory systems as compared to the auditory
system. For example, in their review of the physiology of perception, Parker and Newsome (1998).note that
"remarkably, we have been unable to identify studies of the auditory pathways in which neural signals have
been measured at the same time as the subject is performing at near-threshold levels in a detection or
discrimination task. Although the activity of auditory nerve fibers has received considerable experimental
and theoretical attention, insight into the neural substrates of auditory perception will ultimately require
investigation of the central auditory pathways in the context of specific psychophysical tasks."
Neural mechanisms of sound localization
There is now general agreement that there are three important cues that are used by the mammalian
auditory system to localize sounds: the binaural cues of interaural time (ITDs) and interaurallevel disparities
(ILDs) are important for azimuthal localization while the spectral cues provided by the pinna are crucial for
vertical localization. The classical view (Goldberg and Brown, 1969; Boudreau and Tsuchitani, 1970) that
ITDs and ILDs are first encoded by the medial (MSO) and lateral superior olives (LSO) has largely been
supported by modern studies.
Our lab has played a seminal role in studies of the details of the neural circuitry of. binaural processing.
Yin and Chan (1990) provided a systematic study of the MSO, showing how these cells behave like fine-
time scale coincidence detectors while Yin et al. (1987) provided evidence from the inferior colliculus that
the binaural interaction was similar to the process of cross'correlation. Joris et al. (1994) found the
surprising enhanced phase-locking in the bushy cells of the anteroventral cochlear nucleus (AVCN) which
provide input to the MSO and LSO. Using intra-axonal recording and injection of single axons, Smith et al.
(1991, 1993) described the detailed axonal projection of physiologically-characterized globular bushy cells
to the medial nucleus of the trapezoid body and spherical bushy cells to the MSO and LSO while Smith et al.
(1998) showed the details of the projection of single labeled axons for the inhibitory input to the LSO from
the MNTB. Joris and Yin (1995,1998) found that LSO cells were also sensitive to ITDs ofamplitude
modulated signals which arose as a natural consequence of their sensitivity to ILDs. Tollin and Yin (2002)
used the virtual space technique to provide quantitative support for the classical view that the important cue
for cells in the LSO was ILDs and not ITDs or spectral cues. Along with the work of many other labs
(reviewed in Irvine, 1986; Yin, 2002) there can be little doubt that the binaural cues of lTD and ILD are
established at the level of the superior olive and expressed and elaborated at all other ascending auditory
nuclei: the nuclei of the lateral lemniscus, inferior colliculus, medial geniculate and auditory cortex.
In parallel with these anatomical and physiological studies of the circuitry underlying sound localization,
we have developed a behavioral preparation using operant conditioning in which we can quantify the
Background & Significance Page 33
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Principallnvesligator/Program Director (Last, first, middle): YIN, TOM, C T
accuracy and precision of sound localization of cats by having them orient their eyes to the sound source
with their heads restrained (Populin and Yin, 1998a) or unrestrained (Tollin et aI., 2005). While our cats are
working in this localization task, we have also monitored the movements of their pinnae and found that the
ears are precisely controlled, even though ear position is irrelevant to the reward contingency (Populin and
Yin, 1998b)..
Behavioral studies of sound localization
Studies of sound localization fall into two broad categories: those that measure absolute localization and
those requiring relative localization. Most relative measures involve determination of the minimum audible
angle (MAA), which requires a subject to discriminate a change in the location of a sound source in space
and to measure the minimum discriminable speaker separation (Mills, 1958; Huang and May, 1996). Our
experimental procedures require the cats to look at sound sources and therefore measure absolute
localization. For absolute loc~lization there are also two general classes of experiments: ones in which the
animal is required to start in a fixed location and walk to the sound source ("approach-to-target") and others
in which the orientation of the head and/or eyes is used to determine the localization accuracy. As
discussed below, most of the cortical localization experiments used the approach-to-target task while we
. have used the orienting movements of the head and eyes. Our experimental procedure is similar to the
head-pointing task used by May and Huang (1996), Thompson and Masterton (,78), and Beitel and Kaas
(1993) in cats and Makous and Middlebrooks (1990) in humans except for the very important difference that
we use eye position, or gaze, as the output variable rather than head position. Nodal et al. (2008) trained
ferrets to walk to sound sources but also measured their orienting head movements before they started
moving to the source to compare the accuracy of head movement with their eventual choice of speaker
position.
We believe our choice of measuring eye position is preferable to head position. First, we monitor both
eye and head position so that if the cat looks at the target but does not point its nose at it, we will have a better
monitor of localization. Indeed, our data comparing head and gaze position show that gaze is much more
accurate than head (Ruhland et aI., in prep.) Second, we sample the output of the search coils at 500 Hz
which allows us to accurately study the kinematics of the eye and head movement (Populin and Yin, 1999;
Ruhland et aI., in prep) whereas most head tracking devices sample at 10 Hz. Third, we are able to monitor
movement and position of the pinnae which show large and consistent movements associated with both visual
and acoustic targets (Populin and Yin, 1998b; Tollin et aI., in prep.).
Coordination of eye and head movements to visual (Guitton et al. '84; Blakemore and Donaghy '80; Bizzi
et al. '71; Morasso et al. '73; Goosens and van Opstal, 1997; Bremen et aI., 2007) and auditory (Frens and
van Opstal, 1995; Frens et aI., 1995; Goosens and van Opstal, 1999; Hofman and van Opstal, 2002; 2003)
targets in cats, monkeys, and human subjects has been studied by a number of labs. Since we routinely have
the cat localizing both visual and acoustic targets, as well as bimodal targets, at the same locations, we will be
able to assess the differences between saccades to targets of different modalities. Guitton et al. ('84) found
that the head movement had a shorter latency for most visual saccades, though Blakemore and Donaghy
('80) found otherwise.
While there is consensus that the superior olive and its afferents from the cochlear nuclei are necessary
for sound localization, a critical question for us is what additional circuitry above the level of the superior
olive is necessary for ~he be9avioral or:'~:I~' re~~onse tQsolmds that we have been studying. In partie. ular
we ro ose to etermlne th~~ _~_ :E.."'P:~ 0-'';) ,.
",-1'0
Our general model of rTlmral CIrcuitryTor sound localization IS that the cues for
"'o"'c"'a<lr-iz"'a"'Io'-n"a"r"'e-nrst encoded in separate parallel circuits at the level of the superior olive and this
information converges in the inferior colliculus. From the IC there are two major streams: one, subcortical
prOjecting to the superior colliculus and brainstem motor circuits that mediate the fast orienting movements
of the head, eyes and ears and two, a cortical circuit involving primary auditory cortex as well as other
cortical areas that elaborate acoustic behavior such as approach-to-target locomotion.
Midbrain involvement The midbrain circuitry involving the inferior (I C) and superior colliculus (SC) is a
prime candidate for mediating the orienting responses. The IC receives convergent ascending auditory
information from a diverse collection of auditory brainstem nuclei: the cochlear nuclei, the superior olivary
complex, and the nuclei of the lateral lemniscus. It is thought to be an obligatory relay for information
2011-04-22 000037
Principallnvestigalor/Program Director (last, first, middle): YIN, TOM, C T
ascending to the auditory thalamus and cortex (Aitkin and Phillips, 1984) (see reviews by Winer and
Schreiner, 2005; Cant, 2005; Schofield, 2005). Both the lemniscal and extralemniscal pathways travel
through the various divisions of the IC. Many studies of the physiological mechanisms of sound localization
have been based on recordings from cells in the IC, starting with the classic study of Rose et al. (1966).
Studies in the IC have uncovered many of the fundamental features of binaural processing: the concept
(Rose et aI., 1966) and implementation of characteristic delay (Yin and Kuwada, 1983a), evidence for cross-
correlation in lTD-sensitive cells (Yin et al., 1987), evidence for directional selectivity (Yin and Kuwada,
1983a), and context-dependent interaural phase sensitivity (Spitzer and Semple, 1991). While the major
projections from the IC ascend to the medial geniculate body and then to the auditory cortex, there is
evidence for a diverging pathway to the deep layers of the SC which can mediate orienting responses of the
eyes, ears and head by way of the nucleus of the brachium of the IC (King et ai'., 1998; Nodal et aI., 2005).
The SC is usually considered to be part of the visuomotor system by virtue of the prominent visual input
to the superficial layers from retinal ganglion cells and the saccade-related responses of cells in the deep
and intermediate layers in both the monkey (Wurtz and Goldberg, 1972; Mays and Sparks, 1980; Sparks,
1986) and the cat (Peck et aI., 1980; Munoz and Guitton, 1991; GUitton and Munoz, 1991). There are also
cells in the deep and intermediate layers of the SC that are bimodal (auditory/visual or somath;:/visual) and
arrayed in topographical maps roughly in alignment with the retinotopic maps in the superficial layers .
(Gordon, 1973; Stein et al., 1976; Meredith and Stein, 1983; 1986; 1996; Palmer and King, 1982;
Middlebrooks and Knudsen, 1984, Jay and Sparks, 1984; 1987; Wise and Irvine, 1983; Hirsch et aI., 198(5,
King and Hutchings, 1987; Populin et al. 2004). Furthermore, electrical stimulation of the deep layers can
evoke Short-latency orienting movements of the eyes, head, and ears and the movement vectors are in
rough alignment with the retinotopic maps in the superficial layers (Robinson, 1972; Syka and Straschill,
1970; Schiller and Stryker, 1972; Harris, 1980; Roucoux et aI., 1980; Stein and Clamann, 1981; Schuller and
Radtke-Schuller, 1990; Valentine et aI., 2002). However, as pointed out first by Poppe I (1973), the
alignment of the visual retinotopic map in the superficial layers and the auditory craniocentric map in the
intermediate layers can only hold if the eyes are straight ahead in the orbit. If the eye position is deviated,
the maps will be out of alignment, requiring some compensatory mechanism that relies on an eye pOSition
signal (Jay and Sparks, 1984; 1987; Populin et aI., 2004).
Cortical involvement Ample evidence supports the idea that the primary auditory cortex (AI) plays an
important role in sound localization. Physiological recordings show that neurons in AI are spatially selective
though the receptive fields of AI cells are large and may expand with increasing sound levels (Middlebrooks
and Pettigrew, 1981; Imig et aI., 1990; Rajan et aI., 1990a; 1990b; Clarey et aI., 1994; Brugge et al., 1994).
Most studies of AI have found cells with receptive fields of several different classes: most are tuned to a
portion of the contralateral sound field, some fields are in the frontal region of space, and a minority are
omnidirectional, prefer the ipsilateral field or have complex fields (Rajan et aI., 1998a;1998b; Brugge et aI.,
1996). Middlebrooks et al. (1998) demonstrated that the responses of cortical cells in the anterior
ectosylvian sulcus and secondary auditory cortex (All) can encode the location of a sound source at any
azimuthal angle with varying degrees of accurac usin a neural network decoder. Based on the ev' ence·
above it seems r nable to assume that the . vO vj ~ ""
- ecordings from AI of the<"u:-::n::a:::n::::e""srEetrr.lz:!:e~di-:c:':a~o"=-r':"m:-:o~n:r.e:::y-:-a"'r:::e--:n::oC;:t-=co=m=m::o:::n-;("M;;;e:=rz:::e::nich
n rugge, 1973; Vaadia et aI., 1982; 1986; Schwartz and Tomlinson, 1990; Barbour and Wang, 2003;
Bendor and Wang, 2005; 2008; Sad ago pan and Wang, 2008) and even rarer are recordings made in
animals that are actively attending to and using the sound on a behavioral task (Hocherman et aI., 1976;
Benson and Hienz, 1978; Benson et aI., 1981; Fritz et aI., 2005; 2007; Kalluri et aI., 2008).
The most compelling case that the cortex is involved in localization are studies that have shown
dramatic deficits in sound localization following lesions or inactivation of the primary auditory cortex.
Inactivation of AI by lesions or cooling result in deficits in localization of sound in the sound field
contralateral to the lesion in human subjects (Sanchez-Longo and Forster, 1958; Klingon and Bontecou,
1966), ferret (Kavanagh and Kelly, 1987), and cats (Whitfield et aI., 1972; Jenkins and Masterton, 1982;
Jenkins and Merzenich, 1984; Malhotra et aI., 2004; Malhotra and Lomber, 2007; Lomber et aI., 2007;
Lomber and Malhotra, 2008). The elegant studies using cortical cooling with cryoloops by Lomber and his
colleagues are particularly compelling and leave little doubt that the auditory cortex (AI), posterior auditory
field (PAF) and anterior ectosylvian sulcus (AES) are essential for auditory localization (Malhotra et aI.,
2004; Malhotra and Lomber, 2007; Lomber et aI., 2007; Lomber and Malhotra, 2008). However, the
2011-04-22 000038
behavioral task used in these animal studies has required the cats to do more than just orient to the stimuli;
they have to walk to one of 7 speakers in order to get a reward, the approach-to-target.
Specific aim I From this summary it is apparent that both the auditory midbrain and cortex are
important structures un eri¥ing-.s0Uf1€1-l0GalizationJletlavior..-H0WSVeF,0YI'-aRalysis-Q.W 'e
leads us to hypothesiz
rests lar el on the obs'te-rv-a""'t"""io-n""'t""h-at:r-----....-.<:JL----------------I..'.~'--<
It t e ea res ralne or ree, pinna movemen s are
invariably e-ici e WI t e s ortest atency, WI h means of 25-35 msec (Populin and Yin, 1998b; Tollin et aI.,
2009). Electrical stimulation of the deep layers of the SC evokes pinna movements in the bat with a mean
latency of 16-21 msec (Valentine et aI., 2002) while Populin and Yin (2002) found latencies of auditory cells
in the deep layers of the SC of the awake cat with a mean of 17.7 msec. These numbers suggest little time
for processing to ascend to the auditory cortex and descend back to innervate the pinna muscies in the
facial nucleus. Likewise head movement latencies are generally longer than pinna latencies but in the
head-free cat only lag by a mean of 15.7 msec (Tollin et al., 2009). In specific aim I we propose to examine
k
the role of the auditory cortex and audito midbrain in mediating the orientation behavior in our cats. We
will test the hypothesis that t e ~--- - ----
Thompson and Masterton (1978) studied the brainstem and cortical structures involved in orienting head
movements to sound by making lesions in the brainstem and cortex. They concluded that cortical lesions
did not affect head orientation unless the lesion extended to the most ventral aspect of the auditory cortex
similar to our model. However, they also found that lesions of the SC that abolished visual orienting did not
affect head orientation to sound. One difference between their procedures and ours is that they studied
unconditioned head orienting so the cats were not trained and only a few trials (2-5) were administered per
day and tests were only run every third day. Smith et al. (2004) also reported that head orientation was not
affected by cortical inactivation with GABA antagonist.
~--------~-----------------
_-'i~(llilP3-se.:lQ-ad ess this question by examining
nactivation can be accomplished::i-:::n-;a~n;;;u:;;m="er;-o=wia;::1y~s:;-;:·t~he;::s:;-;e::-ir;:;n:;:;c;;-lu;;:;d;;::e-;s:;-u;;;cTItlo;;-n:::-r:le:;;s"'lo~n~,
coollng;-o:;,J;'~iOsr;ln;;'g;-:d:;;r::u'gs that silence the structure by osmotic minipumps or slow release Elvax capsules
(Smith et aI., 2004). The latter two methods have the advantage of being reversible. The use of cryoloops
to cool and inactivate the cortex has several distinct advantages. The most important is that the inactivation
is reversible so that assessment in the same individual can be made before, during and after cooling. In
addition, the effect is so rapid so that pre- and post-cooling controls can be done in the same session, there
is little chance for developing compensation from other brain areas, the effect can be repeated in the same
animal over many months, and different regions of the brain can be tested in the same individual.
The role of pinna movements in sound localization
Specific aims II and 11/ are directed to studies of the movement of the external ear, or pinnae. It is now
well-established that the acoustic filtering properties of the pinna are important for localization in the vertical
dimension and for monaural localization. The HRTFs in humans and cats both show deep spectral notches
and broader peaks whose location in frequency varies systematically with stimulus position. Distortions of the
pinnae in human subjects result in large increases in absolute errors in elevation judgement and smaller
increases in azimuth (Oldfield and Parker, 1984b; Hofmann et aI., 1998). However, the cat and human pinnae
differ in one important respect: the cat's pinnae are mobile. Movements of the pinnae change the
directionality of the external ear (Calford and Pettigrew, 1984; Middlebrooks and Knudsen, 1987) as well as
the frequency of the notches and peaks in the HRTFs (Young et aI., 1996). Physiologically, pinna movements
can systematically change the responses of neurons in the SC and IC, which is likely a consequence of the
changes in the acoustical cues (Middlebrooks and Knudsen, 1987; Sun and Jen, 1987).
The cat's pinna is innervated by a complex arrangement of 22 muscles, that can move the pinna in a
number of directions as well as change its shape (Crouch, 1969). The motoneurons that innervate the pinna
are located in the facial nucleus and are arranged topographically according to the primary action of the
muscle (Kume et aI., 1978; Populin and Yin, 1995). The pinna motoneuron division of the facial nucleus
receives input from the contralateral paralemniscal region of the lateral midbrain tegmentum (Henkel, 1981;
May et aI., 1990) which in turn receives input from the deep layers of the superior colliculus (Henkel and
2011-04-22 000039
Edwards, 1978, Vidal et aI., 1988). Intracellular recording from facial motoneurons that innervate the pinna
while stimulating the paralemniscal zone show both monosynaptic EPSPs and disynaptic IPSPs (May et aI.,
1990). Stimulation of the deep SC produces discrete pinna movements that are topographically arranged
according to the locus of stimulation (Stein and Clamann, 1981; Schuller and Radtke-Schuller, 1990;
Valentine et al. 2002). The latency of pinna movements to electrical stimulation of the SC was found to be in
the range of 16-21 msec in bats by Valentine et al. (2002), while head movements evoked by the same stimuli
were in the range of 47-99 msec. However, these measurements of latency were done by examination of
individual frames of videos running at 33 or 300 frames/sec so the latencies are likely to be overestimated.
One of the difficulties in studying the pinna is that its position is difficult to measure. Early on; the most
straight-forward method was to video tape the head and ear position, sometimes from more than one camera,
and then study single frames of the ear position with drawings (Heffner and Heffner, 1988; Stein and Clamann,
1981; Valentine et aI., 2002) or simply report the lack of ear movement (Peck et aI., 1995; May and Huang,
1996). Other investigators have also used the search coil technique but the coil was taped on the ear at the
beginning of the day (Hartline et aI., 1995). Jay and Sparks (1987) mechanically restrained the ears of their
monkeys, though no information was given as to how this was achieved, in order to show that the modulation
with eye pOSition in the SC was not due to pinna movement. We have chosen to use a search coil surgically
implanted behind the ear (Populin and Yin, 1998b). This technique has several distinct advantages over the
other methods: the coil has both fine spatial and temporal resolution, it provides a continuous record of pinna
position, it is lightweight with little inertia to interfere with pinna movement, and the calibration does not change
from day to day, as it would if it were taped on everyday.
Several groups have studied the effect of pinna and/or head movements on localization indirectly by
comparing localization of long and short duration stimuli, assuming that short stimuli do not allow pinna or
head movements. Both Heffner and Heffner ('88) and May and Huang (1996) found similar performances of
cats on an MAA and a head orientation experiment, respectively, using both short (40 msec) and much
longer (200 ms and 'continuous') duration stimuli and concluded that movements of the pinnae had little
effect. On the other hand, Jenkins and Masterton ('82) found that monaural localization was improved by
longer duration stimuli, which they attributed to scanning movements of the head or ears. Localization in
our cats improves markedly for longer duration (1000 ms) stimuli as compared with the short stimuli (15 ms)
(Toll in et aI., 2005). While pinna movement may be responsible for this improvement, we can not rule out
an effect of memory for the poorer performance with shorter stimuli. Our measurements show that the
latencies to pinna movements can be as short as 15 msec, with mean latencies of 25-35 msec (Populin and
Yin, 1998b; Tollin et aI., 2009).
The vestibulD'':;-W1~@.q::~~!y!'!b:LSO~u,J!rJdga!1ta~w/J!im.J~head restrained showed that
Since the ears are ph sicall '-o-n""'t"'h-e"7""':e"""''''''-n-d''
move with It, we reasoned than
( ~
\
between Ilia vestibular system and ear movelllellts ill Iheiiterature bu licit descriptions of a VOR-like
reflex since none of the studies were done in behaving animals. Electrical stimulation of the vestibular
nerves produces VAR-like pinna movements parallel to the plane of the canal whose nerve was stimulated
and compensatory to the movements of the head that were induced by the stimulation (Suzuki and Cohen,
1964). Moreover, Schaefer et al. (1971) showed that a post-rotational nystagmus could be produced in the
pinna of rabbits that both mimicked and was in phase with the traditional eye nystagmus and also indicated
that during the initial moment of acceleration of passive rotation in blindfolded rabbits, the pinnae made a
compensatory rotation against the direction of rotation. There is anatomical support for a circuit similar to
that known to underlie the VOR for vestibular activation of the pinna muscles. Shaw and Baker (1983)
described inputs to the facial nucleus from the vestibular nuclei.
During a head-free gaze shift, the ipsilateral pinna makes a very short latency (mean 33.7 ms) saccade-
like movement towards the sound source. Shortly afterward (mean of 15.8 ms) the head and eyes begin to
move. The pinna has reached its final position well before the head, and the ear maintains its new position
despite the ongoing head movement. The only way in which that can happen is if the pinna counter-rotates
on the head to compensate for the head rotation. The VAR is maintained even when the head is passively
2011-04-22 000040
moved during the course of active fixation of the sound, thereby ruling out efference copy as a source of the
compensatory ear movement (Tollin et aI., 2009).
There are few recordings from cells related to pinna movements. Siegel et al. (1980) recorded cells
whose discharge was related to pinna movements from the pontomedullary reticular formation in the cat.
Siegel et al. (1983) described 22 cells (7% of their sample) that discharged in relation to movement of the
ipsilateral pinna. However, since they did not have the ability to actually show pinna movement, they could
only describe qualitatively the relationship between pinna position and discharge rate. These 'pinna cells'
were found scattered over a large area of the medial reticular formation.
I II establish that the VAR is driven b vestibular input, aim lIa ro ose
nactivation 0 t eves I u ar system has usually been

accomplished eit er by a la ryinthectomy or plugging of the semicircular canals. Plugging of the canals has
less chance of influencing cochlear function and it has been found to be most effective for low frequenc.p,·""s_,
. hi h fre uen .e less affected Lasker et al. 1999. If this is the case, then we mi ht find tha
~ Ince we un ers an many 0 t e details of the oculomotor circuitry, the

':,pT.ln:-:n:-;a'"'m=or.to:-:r-::s::Cy:::;stC:e::::m~m:-;a::-y:-:s:-;e:-:rv"'e~a=-s a bridge to understanding other systems. There are many intriguing
parallels between the oculomotor and pinna motor control systems. Both point the sensory apparatus
towards objects of interest, either visual or acoustic. The pinna movements are saccade-like in their speed
and accuracy so it is likely that the motor control signals are similar. Since both are physically located On
the head, they have developed compensatory mechanisms, the VOR and VAR, to stabilize their position
despite the presence of head movements. Neither system needs to deal with a changing load. However,
the control of the pinna muscles is more complex than that of the ocular muscles given that more muscles
and more degrees of frEffldom are involved. byt it is likely, simpler than that of other skeletal muscles,
especially if we find thaL at: jl\nother major difference between the oculomotor
and pinna motor systems is that pinna movements are independent in the two ears while vestibularly-
evoked eye movements are conjugate.
While the oculomotor system has been studied intensively for over 40 years, so that it is without doubt
the motor system that we understand the best. we know almost nothing about the control of the pinna. Aim
III is designed to begin filling in this void by studying the circuitry underlying pinna movements in the
brainstem. There are very few studies reporting a relationship between neural activity and pinna movement
(Siegel et aI., 1980; 1983). Studies of the neural circuitry underlying activation of the motoneurons in the
facial nucleus that innervate the pinna muscles has concentrated on the paralemniscal zone of the lateral
midbrain (Henkel, 1981; May et aI., 1990) which gets input from the intermediate layers of the SC (Henkel
and Edwards, 1978; Vidal et aI., 1988). We are not aware of any study that has recorded from facial
motoneurons while monitoring pinna position. A difficulty in earlier work was the absence of any monitor of
pinna position. Since we measure pinna position with the search coil, we are better equipped to show the
relationship between the discharaa()f """&.and pinna m()vement Since the Dinna m .
like aim ilia hYQ.othesizes th~
Most skeletal muscles are richly innervated with muscle spindles and Golgi tendon organs that have
monosynaptic or disynaptic connections to the homonymous motoneurons and provide the. well-known stretch
reflex. There are muscles that do not show a stretch reflex and/or have muscles spindles which are unusual in
shape: the extraocular muscles, muscles of facial expression, muscles important for speech (Keller and
Robinson, 1971; Neilson et al., 1979; Folkins and Larson, 1978). A characteristic common to these muscles
that lack a stretch reflex is that they naturally never face a changing load. Pinna muscles would also fall into
2011-04-22 000041
Principallnvestigator/Program Director {Last first, middle): YIN, TOM, C T
this category so aim IIIb hypothesizes tha -:1/

r't-
described proprioceptive inputs from the pk.n"'a-';::o""""'ctorsarccrCh! nuc eus a e r Insensitivity to
touch and hair deflection and sensitivity to vibration and muscle stretch suggesting the presence of muscle
spindles on pinna muscles.
There is little information available on the extent to which animals with movable pinnae actually use the
mobility for accurate sound localization. Mogdans et al. (1998) found that immobilizing the pinnae of bats
working in a wire avoidance task produced significant changes in their ability to avoid /lorjzontal but not
vertical wires. The inability to avoid horizontal wires presumably results from errors in localizing in the vertical
dimension during active echolocation. Heffner and Heffner ('82) described an elephant who held its pinnae in
a stereotyPEld and unusual position when localizing sounds. Heffner and Heffner ('88) videotaped cats while
performing a MAA task for speakers opposite the right ear, and found that the right pinna turned toward the
speaker while the left pinna position varied; and when localizing speakers straight ahead, both pinnae were
facing forward. May and Huang (1996) did not measure pinna movements in their procedure but did report
that informal monitoring with a video camera indicated that the cats adopted a stable alert posture while
awaiting the orientation stimuli and did not move noticeably. Similarly, Peck et al. (1995) reported negligible
pinna movements as monitored by a video camera in a task similar to our fixed-head preparation. In sharp
contrast to these results, we measured consistent and reproducible pinna movements during our head-fixed
(Populin and Yin, 1998b) as well our head-free (Tollin et aI., 2009) sound localization task. The movements
were easily seen in video images and quantified by a search coil sutured subcutaneously on the back of the
pinna (Populin and Yin, 1998b). A possible explanation for these differences is that our cats were extensively
trained while the others were only required to make eye movements in the general direction of the target.
Although Hartline et al. (1995) also report pinna movements, it is difficult to interpret their observations
since their procedures are not clearly articulated: they attached the pinna coil to the ear each day before
recording, do not describe any procedure to calibrate their pinna coil, and do not indicate how stationary the
coil was on the ear as it moved from trial to trial. Furthermore, their cats were not trained so that the
experimenter did not have control of eye pOSition. By implanting the pinna coil subcutaneously to the ear, we
minimize any chance that the coil will slip on the ear during the fast pinna movements and we calibrate the
pinna coil when the cat has its ears held in the upright alert position while waiting for the fixation LED to
appear. Aim IIle will study the effect of immobilizing the pinnae on sound localization in our behavioral task.
Immobilization ill be aceom lished b denervatin the inna muscles as outlined in Po ulin et al. 2004.
We ex ect that
2011-04-22 000042
Principallnvestigator/Program Director (Last, firsl, middle): YIN. TOM, C T
C. PROGRESS REPORT
This progress report covers the period of our previous grant application from 3/2004 to 3/2009. This grant
had two specific aims: first, we proposed to continue our psychophysical and physiological studies of sound
localization in the awake behaving cat preparation, in particular by using two auditory spatial illusions, the
precedence effect (PE) and the Franssen effect (FE) to test the hypothesis that the inferior colliculus is involved
in the neuronal representation of spatial sound localization and second, to develop a new behavioral test of
selective auditory attention to test the hypothesis that cells in the auditory cortex are involved in selective
attention. Considerable progress was made on specific aim 1 as detailed below but despite extensive effort for
3 years we were unable to convincingly train the cats on the selective attention task so we reluctantly aban-
doned this aim. Instead, we focused our efforts on an exciting new discovery of an important localization
reflex made during this grant period, the vestibulo-auricular reflex. In the summary below, new papers resulting
from this grant period are shown in bold and listed in section
Eb)
Sound localization behavior
One of our important achievements over the last decade
is the development of a consistent behaving cat preparation
based on sound localization performance. Our initial psy-
chophysical measurements of localization with the head
restrained demonstrated the ability to train cats to look at
light and sound sources, but localization of auditory targets
was significantly less accurate and less precise than to
visual targets, with severe underestimation of eccentric
.10' o,,~
positions (Populin and Yin, 1998a). However, when we used
·20 • Target ..~, ..
the more natural situation with the head free, the localization .30 R~'spq!1se
A
of the eye in space, or gaze, improved dramatically so that it -30 ·20 ·10 0 10 20 30 -30 ·20 ·10 0 10 20 30
was virtually the same as visual localization (Tollln et aI., Azimuth (deg) Azimuth (deg)
2005a). The importance of using an ethologically natural 30 ,-- .
behavior was underscored by. the Editorical Focus article by C) ., [C
~
Sparks (2005) that accompanied our paper. Figure 1 com-

-"
Q)
pares head restrained (left) and head free (right) localization 10 !

c:
0
of auditory targets within the oculomotor range (±25°) of the
~
o
cat showing several different ways in which we analyze the 6= 2.81
GaIn ~ 0.81 --!
data. Fig. 1A shows the horizontal eye position traces as a iii -20
n = 312
.30~ .-
function of time. The cat fixated an LED straight ahead until -"---'-"--~'~-r~ .~' ,~;
time 0, at which time the acoustic target was turned on. The "'iO o /
position of the four targets and the size of the electronic

mQ) , "', ,
~
0'
"
window used to reward the cat are shown by the small ::E. 10 ~ ,
horizontal arrows at the right. Fig. 1B shows the data :S o·
" 0,,1.92
~
·10 t
displayed as scatter plots of final eye position for the 8 , y- Gain .. 1.02
targets. The position of the target is shown by the large -20! / GaIn = 0.52 n:318
shaded symbol while saccades to that target are shown by -3otc~ . !!." 3~~ /
·30 .20 ·10 0 10 20 3J -30 -20 .10 0 10 20 30
small unfilled symbols of the same color. Accuracy and Motor Error (deg) Motor Error (deg)
precision of localization were quantified by the gain (or
slope) and residual error (0), respectively, of the saccade Fig. 1 Comparison oflocalization peljormance with head
or gaze amplitude vs motor error plot, computed sepa- restrained (left) and head Jree (right). A: Horizontal eye
movement traces to 4 targets (small arrows on the right).
rately for the elevational and azimuthal components of the
B. Two dimensional scatter plot offinal eye and gaze posi-
movement (Fig. 1). The accuracy and precision of our
tion/or 8 targets on the horizontal and vertical meridians.
cat's localization is comparable to and, indeed in most Targets are indicated by solid symbols and single trials to
cases superior to that of human subjects and barn owls, those targets by corresponding open symbols. C:
two other model systems for sound localization. See Acccuracy ofsaccades and gaze shifts to "el1ical (top row)
Tollin et al., 2005b for a discussion of the use of the and horizontal (bottom row) targets plotted as movement
terms precision and accuracy in response to a Letter to amplitude vs motor errOl: From TolUIl et al., 200Sa
Preliminary Studies/Progress Page 40
2011-04-22 000043
Principallnvesligator/Program Director {Last, first, middle}: YIN. TOM, C T
the Editor from Heffner and Heffner (2005). Fig. 2 shows a com-
parison of our results in the cat (top) with the barn owl (Knudsen et
aI., 1979), and two studies with human subjects (Makous and
Middlebrooks, 1990; Recanzone et aI., 1998) all plotted on ap-
proximately the same scale. For the data from Makous and
Middlebrooks (1990) the circles represent 1 S.D. of the 6 trials ar
each point and were obtained in open-loop, i.e. with long-duration
stimuli.
Behavioral studies of sound localization typically employ
either relative or absolute tasks and it is widely thought that one
can relate relative measures of localization acuity, such as the
minimum audible angle (MAA), to the precision of absolute local-
ization (see Heffner and Heffner, 2005). It seems natural to think
that the ability to discriminate between two sounds differing in
spatial position must be related to our ability to localize those
sounds on an absolute scale. However, despite a general corre-
spondence between absolute and relative psychophysical mea-
sures (Makous and Middlebrooks, 1990; Recanzone et aI., 1998),
there are several examples of severe departures between them.
For example, humans have repeatedly been measured to have
MAAs near 1°for both low- and high-frequency pure tone stimuli
from directly ahead with much larger MAAs to the side (Mills,
1958; Blauert, 1983), yet subjects who are required to actually
indicate the spatial location of such stimuli often display large
variability and poor accuracy in their responses with little or no
spatial dependence (Stevens and Newman, 1936; Oldfield and
Parker, 1984a; Wightman and Kistler, 1994; Middlebrooks, 1992).
To address this issue, we estimated MAAs from the precision
of our absolute localization (Moore et aI., 2008). We found
that measures of MAA were indeed related to the precision
of the localization estimates but only if we also took into
account the accuracy of the estimates.
With the head free,cats localize targets with gaze shifts
that consist of a combination of eye and head movements.
We have studied the kinematics of the eye, head and gaze
shifts made by cats towards visual and acoustic targets (Fig.
3). In the cat the gaze shifts consist of a head movement
that usually accounts for about 50-70% of the gaze shift.
Unlike in the primate, often the head will move first. The
main sequence of head and gaze shifts for visual and acous-
tic targets are comparable in most cats. The minimum
latency of gaze shifts for acoustic targets is shorter than for
visual targets though the distribution of latencies is quite
variable from one animal to another.
We have studied the effect of the stimulus spectra on
localization as a way of demonstrating the role of pinna filterin
on vertical localization. We compared the ability of cats to
localize broad band and narrow band signals, including narro .
band noise and tones. The general result was very consistent ------'
and compelling: cats were unable to localize narrow band stimuli In the verhcal dimenSion while onzontal
localization was not as precise but reasonably accurate. Fig. 4 compares localization of broad band noise with
a 500 Hz pure tone. Tones up to 14 kHz were also tested a,nd all of the results were similar to that shown.
2011-04-22 000044
Principallnvestigator/Program Director (Lasl, first, middle): YIN, TOM, C T
Likewise localization of narrow band noise was also poor in the

vertical dimension (not shown).
Spatial auditory illusions Sensory illusions have often been
used to probe the operation of the nervous system. When percep-
tion is not congruent with what is expected based on the physical
stimulus, it can provide clues to how the brain encodes the stimuli. I
We have made use of two spatial auditory illusions, the prece- \
dence effect (PE) and Franssen effect (FE), to probe the neural )
representation of auditory space. Our previous work had shown
that the cats experienced all three components of the PE, namely,
I
!
summing localization, PE or localization dominance, and echo
threshold, in a manner similar to that of human subjects (Populin
and Yin, 1998a; Tollin and Yin, 2003a; 2003b). Moreover, mea-
surements of the movements of the external ear, or pinnae, were
consistent and systematically directed towards the targets, either
visual or acoustic (Populin and Yin, 1998b). Tollin et al. in re
took advantage of these two results to examin
i
/
i
mimic mg e I h their heads unrestrained,

localization was more accurate (Dent et aI., 2005). .
We have focused our physiological studies of the PE on cells in tl1eirlfeliOl col· arller studies
in the IC of anesthetized animals had found correlates to summing localization and localization dominance in
responses of IC neurons reflected as suppression of the responses to the lagging sound. The strength of the
suppression varied with the interstimulus delay in a manner similar to the behavioral suppression (Yin, 1994;
Litovsky and Yin, 1998a; 1998b). However, our estimates of echo threshold were significantly longer than those
2011-04-22 000045
Prindpallnvestigator/Program Director (Last, first, middle): YIN, TOM, C T
found in the Ie of the awake rabbit (Fitzpatrick et aI., 1995),

Tollin et al. (2004) examined this discrepancy by measur-
ing the suppression as a function of interstimulus delay
and found that echo thresholds measured in our awake cat
preparation were closer to those described in the awake
rabbit (Fig. 7), thereby implicating anesthetic, rather than a
species difference, as the critical factor.
This study
While most physiological studies have focused on the FItzpatrick et al ('SSe
temporal dynamics of the recovery curves, there has been Yin ('94)
'-~
little attention paid either psychophysically or physiologi-
cally to the effect of the actual location of the speakers on
r
o 10 20 30 40 50
the stren9,th ,of suppression. We have examined this by ISD (msec)
studyinruneJ \ Fig. 7. Anesthetic prolongs lag recoveJY times for PE
,t --';>
,
;t stimuli. Mean normalized population recove,)' Clln'es for
awake behaving cats are similar to those in unanesthetized
rabbits (Fit7potrick et 01., 1995) alld shorter than those ill
:... t a;..I.~,2~O.;O..:.4~_d,
With the ISD set near the echo threshold (20 111.5)-, w""e"-"-'t,o",u"-n,,,d,,-J,.:0..."_eS:.::ti.::!e.::ti:::ze:.::d:.::c.::ot:.::s.:. (Yi:.::m.:. ,.:.1:.. :99__4.::.).:.::F.:.ro.::n:.::'.:.To:.. :l.::lin::.. .:. e..
'::'i r-~th",a"",,jj
Another spallal IllUSion mal we nave stualea IS me r-ransse l

effect (FE), a striking auditory illusion showing the importance
of stimulus onset previously demonstrated only in humans. To
elicit the FE, subjects are presented with two spatially-separated
sounds; one a transient tone with an abrupt onset and immediatf
ramped offset and the other a sustained tone of the same fre-
quency with a ramped onset which remains on for several hun-
dred msec. The FE illusion occurs when listeners localize the
tones at the location of the transient signal, even though that
sound has ended and the sustained one is the only one present.
The FE illusion occurs most readily in reverberant environments
and with pure tones of ~2 kHz in humans, conditions where soun::d"l;::o"'ca:::;llrr:,lz:-::a"'tll""'o=n"""ls"""a"II"'ff"-ic::-:uJrlt"in::-Ch7":u=m::a:::n:::s-.=
wle'"'t"'co"'u:::n-::r-
a --"
that cats also experience the FE, though the tones that are most effective are higher in frequency than for
human subjects, corresponding to the frequencies at which cats have difficulty localizing (Dent et al., 2004).
Vestibulo-auricular reflex (VAR) Probably the most important finding made during the previous grant period
was the discovery of a reflex (Totlin et al., 2009) that we have called the vestibulo-auricular reflex, or VAR, in
analogy to the very well-known vestibulo-ocular reflex (VOR). Like the VOR, the VAR appears to compensate
for movements of the head by counter-rotation of the pinna on the head. Fig. 9a shows the movements of the
head (black), left ear (blue), ear-on-head (red), and gaze (green) during a head free gaze shift to the target 30°
to the left. Note that the pinna moves first, making a quick saccade-like leftward movement towards, but usually
short of, the target. Shortly afterward, the head and gaze move toward the target with the head moving with a
slower velocity. The salient point is that as the head continues to move leftward, the pinna, having achieved its
final position, remains more or less stable in space, despite the fact that it is resting on the head. In order to do
this, the pinna must counter-rotate on the head to compensate for the head movement. The counter-rotation is
most easily seen by the ear-on-head trace in Fig. 9a.
2011-04-22 000046
Principallnvestigator/Program Director (Last. first, middle): YIN. TOM, C T
To quantify the gain of the VAR, we adapted a method used in studies of the VOR (Huterer and Cullen,
2002) and calculated the ratio of peak ear-on-head velocity to peak head velocity during the VAR (shaded in
Fig. 9b). The times of the peak velocities are indicated by the small tic marks on Fig. 9b. For the example
shown, the gain was -0.85. Perfect compensa- a 10 C
tion would be a gain of -1.0. We refer to the g> o~ ~==t. '~'W~"
40 -1
gain calculated in this way as the Active VAR os
5 ·10
since the cat is actively moving its head. Figs. 1;l
lelt-€~f
20 -j
9c and 9d show that the VAR does not function 8. -20 /
for a similar head movement in the contralateral

3D
i- .." L E"~~h,"
0
direction. For the target 45 to the right, the left £ ·4050 ~,.",,'n_....... 0 $18.135
{:,~~:t:====
243A
ear simply rides on the head and the ear-on- b - -200 ·100 0 100 200 300 4DC d-200 o 200 400
head trace is essentially flat with no com pens a- 200 200
tion for head movement. The VAR was also
present for visual targets that had no acoustic
component. On average, the peak ear-on-head Ear-on-head
velocity occurred 9.7 ms (n = 149) after the
peak head velocity. For our sample of Active
VAR movements from 4 cats, the mean gain
was -1.03. Hence, the pinna movements ap- -200 -100 0 100 200 300 400 ·200 o 200 400
Time re: head movement onset (ms) Time re: head mOV6lmlnt onset (rnsec)
pear to compensate for the head movement.
Although the present data are consistent Fig. 9: Pinna movements compensate/or head movements via the VAR. a.
with a vestibular origin for the VAR, we also Head, left eat; ear-in-head and gaze movements in response to an acoustic
target at 45" to the left. b. Velocities of head alld ear-in-head for the same
considered mechanisms other than vestibu-
trials as in o. c and d. Corresponding traces as in a and b except for a target
lar. Given the short latency of the reflex
45" 10. the right. From Tollin et 01., 2009.
which would rule out proprioceptive feed-
back, the most likely alternative is that the
VAR results from an efference copy of the head movement signal
a
~ 20
that is also sent to the pinna muscles to compensate for the im- :3
pending head movement. To address this possibility, we examined
the VAR while passively rotating the cats during active sound o-~~.
localization. During passive head rotation there is no head move-

ment command and therefore no possible efference copy to the Head
ears provided the head moves with the platform.

A difficulty in passively rotating the animal is that in some trials .40 G03363.{;4
cats will move their heads to counteract the rotation of the body, ·600 ·400 ·200 0 200 400 600
the vestibulo-colic or cervico-colic reflex. We found that some b
animals had a very strong reflex so that the head almost never 200
rotated with the platform while other individuals showed the reflex
only occasionally. So we had to choose trials in which the head i;l
rotated with the platform to avoid this difficulty.
Figure 10 shows one trial in which we passively rotated the cat
i
-
.~ -200
while it was localizing a sound source. In this trial, as in most of g
our experiments of passive VAR, there are two distinct phases: an ~ -
-400 ~
ActiveVAR Passive VAR
Active VAR while the cat oriented its eyes, ears and head to fixate
the acoustic target and a Passive VAR during platform rotation. -600 -400 -200 0 200 400 600
Fig. 10 shows that the active phase of the VAR is similar to those Time re: platform onset (ms)
shown in Fig. 9. When the acoustic stimulus was turned on at-
30 0 (vertical arrow), the pinna and head were both oriented near Fig. 10. The VAR persists durillg passive head ro-
0 0 • The pinna responded to the target first, making a quick left- tatioll. o. Head, left eO/; ear-oil-head, gaze and
ward movement towards the target with a latency of 24 ms, platjonn movementfor a larget 30 °to the left which
followed 16 ms later with a leftward head movement which was turned on at the red arrow. b: Velocities of
triggered the Active VAR and the counter-rotation of the ear-on- head, ear-on-head and eye-on head for the trial
ill a. From Tollill et a1., 2009.
2011-04-22 000047
head (Fig. 10b, shaded). The gain of the Active VAR in Fig. 10 was -1.16 and peak ear-on-head velocity oc-
curred 18 ms after peak head velocity (tics). The pinna maintained its new position when the platform began
moving at t = O. During the Passive VAR (shaded, from ~100 to 600 msec in Fig. 10b) when the platform
moved to the right, both the ear and gaze position remained stable in space due to the VAR and VOR, respec-
tively (Fig. 10a). The counter-rotation of both the ear and eye to compensate for the passive head movement
are apparent in the velocity traces of Fig. 10B during the Passive VAR. Because the passive rotation resulted
in small and flat head velocity profiles with ill-defined peak velocities, we calculated the gain of the Passive
VAR by computing the ratio of mean ear-on-head velocity and mean head velocity. The Passive VAR gain for
Fig. 1OB was -1.00, while the mean Passive VAR gain for all 4 of our cats was -0.89. The presence of the VAR
for passive head movements shows that the VAR cannot be due to an efference copy signal from the head
motor command and strongly implicates the vestibular system as the origin of the VAR.
Physiological studies of sound localization We have continued our studies of the neural mechanisms of sound
localization. The lateral superior olive (LSO) is traditionally thought to be involved in computing interaurallevel
disparities (ILDs) since it receives excitatory input from the ipsilateral cochlear nucleus from spherical bushy
cells and inhibitory input from the contralateral side from the medial nucleus of the trapezoid body (MNTB).
However, the classic studies of the LSO (Boudreau and Tsuchitani, 1968; Guinan et al., 1972b;
Tsuchitani, 1977) claimed that neurons in the lateral low frequency limb were monaural. By contrast, we found
that low frequency LSO neurons were binaural and had IE (input from the contralateral ear was inhibitory and
ipsilateral ear input excitatory) response properties, like their high frequency counterparts (Tollin and Yin,
2005). These neurons displayed all of the properties expected of low frequency IE cells: they exhibited en-
hanced phase-locking to ipSilateral CF tones like their spherical bushy cell input, they showed characteristic
delay with a characteristic phase near 0.5, and their response to ipsilateral stimulation was suppressed by
raising the level to the contralateral ear.
A critical neural structure on the 'motor' side for our sound localization behavior is the superior colliculus
(SC), which is considered to be important for visuomotor processing. Many studies have shown multimodal
cells in the deep layers of the SC with evidence for spatial maps of visual, auditory and somatic space that are
in approximate alignment: cells in the rostral SC
encode visual and auditory space directly in front A ,, (I;l
of the animal while cells located further caudally "
" ,',
,",
represent the contralateral field. However, this ""
alignment only holds when the eye is directed cen,erp Ri9h'!!j!J,
straight ahead. If the eyes move, then the
alignment no longer holds (Poppe I, 1973).
Populin et al. (2004) studied the effect of eye b~::lu:
position on responses to auditory stimuli in the ~~.,.
,:' \,
SC of the awake, behaving cat. The goal of the ,.f.;t' : ',,""
11111 ,
, ':"', .I"
experiment was to resolve a controversy about
~" 2°1
whether cats show the motor error model of
oculomotor coordinate transforms previously
shown by Jay and Sparks (1987) in the monkey.
Ill,
It: "" .,,~,., ". ,I,"
.800 .400 0 ~oo 800
rlffie(msec)
·800 ·400 0
1... ,",
400 800
TIme (msec)
L.,. ,
·800 ·400 0
TIfM (msec)
~'.
I" 400. ,800
Harris et al. (1980) had reported no modulation
of responses to acoustic stimuli as a function of 15
eye position in the cat, contrary to the results of 10
Jay and Sparks (1987). We recorded from cells
5
in the deep and intermediate layers of the SC
while the cat localized visual and acoustic o L--",,~=~--.J
·50 0 50 100
Horizontal Mowr Error (<leg)
stimuli. The stimuli were delivered while the cat
fixated an LED while working in the sensory Fig. 11. A: Responses ofa cell in the left SC to a speaker 63 °to the right
probe task, where the fixation LED remains on at three different eye positionslLeft, Center alld Right). B: Response of
signaling the cat to keep fixating it despite the the same cell as afimction of speaker position while fixating at three eye
positiollS. C: Same data ill B plotted as a junction of the difference
presence of another stimulus (Fig. 13). By
between eye and speakerposition, or motor error. Adapted/rom Populill
changing the pOSition of the fixation LED we
e/ 01., 2004.
could explore possible modulation of responses
2011-04-22 000048
PrincipallnvesHgator/Program Director (Last, first, middle): YIN, TOM, C T
to identical acoustic stimuli by eye position. Fig.

11 A shows responses of one cell during fixation 3 3
A 6 B
at 3 different positions to the same acoustic
stimulus. The stimuli in all three cases were
identical and delivered from a speaker 63° to the 0:>
2
1
0
00
0
... .,.
right. There is a clear dependence on eye posi-
6
R· htward MEl Rlghtward MEl
6
•
tion such that the strongest response was ob- -3 ·2 -1 2 3 -3 -2 ·1 2 3
tained when the cat was fixating furthest from the -1 v ·1 v
o Cat6
iil
LED. This is in accord with the motor error -2
iil
~
o Cat7
f::" Cat19
-2 "
1.'l"
.
I"
v Call1
hypothesis and is summarized in the plots of o CattO
v v
discharge rate vs speaker position for each of -3 + Mean -3
the 3 eye positions, left (L), center (C), and right
Fig. 12: summmy of the modulation of SC cells by eye position using
(R) (Fig. 11 B). The data points indicated by the the motor error index (MEl). A: leftward MEl plolled asjunction of
arrow are those shown in Fig. 11 A. When the rightward MEl computed by taking into account the horizontal RF of all
same data are plotted against motor error 28 neurons studied with mUltiple speaker positions in 5 cats. Bo'
(difference between eye pOSition and target similar plot of MEls computed by faking into account just the medial
position), the three functions nearly superim- edge of the nelllvns' RFs lfilled symbols); open symbols replot those
pose, suggesting that cells in the deep SC MEIsfrom Afmm neumlls that did not have peaked RFs. The standard
encode motor error rather than the spatial error bars represent 95% CIs for the mean MEls. From Populin et al.,
location of the target in space. 2004.
The degree and direction of modulation by eye position is summarized in Fig. 12 using the motor error index
(MEl) which is a measure of the shift of the receptive field by eye position (Populin et al., 2004). By plotting
leftward MEl as a function of rightward MEl, a cell that completely compensates for eye position will have an
MEl of 1.0 and the mean population should be at (1,1). No compensation will be at (0,0) while inverse com-
pensation at (-1,-1). The mean of our population in Fig. 12A is (0:65,0.66). When only the medial edge of the
receptive field is taken into account (Fig. 12B), the mean is at (0.81, 0.48) which is comparable to the 54% shift
measured by Jan and Sparks (1987) using the medial edge.
Since we had shown that the pinnae are mobile and ear position depends on eye position (Populin and Yin,
1998b), there was the possibility that the modulation seen in Fig .. 11 could be due to changes in acoustic input
resulting from pinna movement. As a control we denervated the pinna muscles in one cat and showed that the
modulation with eye position was still present in the SC even when the ears are unable to move.
There has been a recent resurgence of interest in the neural mechanisms underlying ITO encoding. For
many years the Jeffress model was generally accepted as the prevailing model as it could be made to fit most
psychophysical and physiologial data. However, there were actually few physiological or anatomical studies
that addressed the model critically (see Joris et aI., 1998). A key assumption of the model is coincidence
detection by cells in the medial superior olive (Goldberg and Brown, 1969; Crow et aI., 1978; Yin and Chan,
1990; Batra et aI., 1997; Spitzer and Semple, 1998; Brand et aI., 2002). We re-examined this issue by compar-
ing data from two studies in the MSO with a computational model of coincidence and found that the cells did
not behave like an ideal cross-correlator (Batra and Yin, 2004). The more controversial assumption of the
Jeffress model is how internal time delays are established. Jeffress proposed anatomical delay lines, for which
there is some anatomical support from our lab (Smith et aI., 1993) and others (Beckius et aI., 1999). More
recent work suggests that inhibitory inputs to the MSO are important (Brand et aI., 2002; Pecka et aI., 2008)
and this topic was the subject of a review article in TINS (Joris and Yin, 2007).
Summary of progress We have made several important discoveries in the last few years about the neuronal
systems that mediate the cat's sound localization circuits:
1. an exciting new discovery of a previously unknown reflex movement of the external ears which we call
the vestibulo-auricular reflex (VAR)
2. the demonstration that cats perceive auditory spatial illusions such as the precedence effect and the
Franssen effect in the same way as human subjects
3. recordings from the inferior colliculus of behaving cats to stimuli that mimic the precedence effect show
2011-04-22 000049
responses highly correlated with the eat's behavior

4. the discovery that the pinna movements are also highly correlated to behavior when the cat is experi-
encing the PE illusion
5. that unexpected mislocalizations can provide insights into the cues used for localization
6. the demonstration that with the head free the localization ability of cats is equal to or even better than
that of human subjects or barn owls, the other major model systems for sound localization
7. the demonstration that low frequency cells in the LSO are not monaural, as several classic studies
indicate, but rather they are very much like their high frequency counterparts
8. support for the modulation of auditory receptive fields in the eat's SC by eye position in line with the
motor error model previously shown in the monkey
. 9. evidence that anesthesia effects the temporal dynamics of responses and the importance of using
recordings in unanesthetized animals if the goal is to relate physiology to behavior
2011-04-22 000050
PrincipallnvesUgator/Program Director (Last, first, middle): YIN, TOM, C T
D. RESEARCH DESIGN AND METHODS

General surgical and behavioral procedures
All of the surgical procedures are done under aseptic conditions in a surgery suite provided by the Animal
Care Facility. The cat is anesthetized, initially with Ketamine (20 mg/kg, 1M) and Acepromazine (0.2 mg/kg)
and maintained with isofluorane anesthetic (1.5 - 3 % mixed with oxygen) delivered through an endotracheal
tube. A dental acrylic cap is anchored to the skull by 8-12 titanium screws into the bone and a stainless steel
head post is buried in the dental acrylic. The head post is used to hold the head in head-fixed animals and to
hold the feed tube in head-free animals. Care is taken to minimize disruption of the normal mobility of the
pinnae. The eye coils are three turns of fine FEP-coated, stainless steel wire (Alan Baird Industries) with a
diameter of 18-19 mm that are sutured under the conjunctiva of both eyes (Fuchs and Robinson, 1966; Judge
et al. '80). Both eyes are implanted to provide a backup coil though only one is used at a time, i.e. we assume
conjugate eye movements. In addition 10 mm diameter coils with 6 turns of wire, embedded in the coronal
plane in the acrylic of the head implant and implanted subcutaneously behind each external ear, are used to
monitor head and pinna movements as in Populin and Yin (1998a, b). The leads for all the coils are led sub-
cutaneously to connectors that are imbedded in the dental acrylic cap. The coils are connected to a magnetic
search coil system (CNC Engineering) that permits the vertical and horizontal components of the eye, ear and
head movements to be monitored. Special care is taken postoperatively to prevent infection and pain.
The cats are trained by classic operant conditioning using food deprivation and reward. They are food
deprived for 6 days/week and given food ad libitum one day each week to guard against overdeprivation. We
monitor body weight daily to ensure that it remains within 15% of the original weight. On each successful
trial they receive a small drop of pulverized cat chow mixed with water to a consistency of soft paste delivered
to a feeding tube near their mouths. The cat's behavior is routinely observed by video monitors. Initially, the
digital acceptance window is large and the required fixation time short. The aim of the training is to achieve
consistent performance of 80% correct with fixation times of 2-3 seconds and error windows of ±3°.
Mislocalizations can be due to perceptual or motor errors. We use localization to visual targets as a way to
gauge the motor errors; thus differences between localization of visual and acoustic targets reflect errors in
sound localization.
The cats can be run with their heads fixed or head free. Typical acoustic stimuli are chosen to be easily
localized: usually wideband (.1-30 kHz noise bu click train (10 j.lsec duration at 5-10/sec) though~
are also doin ex eriments wit Tollin and Yin, 2003a; 2003b; Tollin et al., 2004~
'It he level of the acoustic stimuli is
~"'a"b;;:o;;-u;'-t"3j'[0-J!6:rOo;a'llB:G;ahbo;;;v"'e~be01h;;;a"vn.lo"r"'all1t"'h"'re"'s"h"'o.illdl-a'"n'"d'l""TOls"r"'o"veo;a;r;:;o"veo.r;"'1f70'L_7J20fT7;..,Jfor each individual trial as described
below. The speakers can be placed in the frontal hemifield from ±90 ° in azimuth and ±60 ° in elevation at a
spacing of 10°.
Acoustic delivery All acoustic stimuli are generated by a Tucker Davis system that is controlled by a Dell
Precision 650 PC computer, a National Instruments AID board, a Keithley digital I/O board, a VC33 DSP for
precise event timing, and pairs of RP2, PA5 and SA1 modules, a PI5 PCI interface, assorted power
multiplexers and Zbus racks from TOT. We can vary the frequency, intensity over 80 dB, phase, duration,
repetition rate, rise/fall time and time delay of the stimuli on two channels independently. In addition to
delivering tones and clicks, the system also contains two general waveform buffers of 2 Mbytes that can
deliver any arbitrary waveform from computer files, and can synthesize amplitude or frequency modulated
signals with any signal as the carrier or modulator. We also have a TDT Medusa system with a RA 16
headstage and amplifier with 4 RA16 Base Stations, 2 RP2 processors, speaker amplifiers, and a P15 PCI
interface board with OpenEx and Open Developer software.
Sound localization training and experimental tasks
Cats are initially trained on the fixation task, which requires that the cat look at LED1 or the SPKR (Fig.
13A). The stimuli, which could be visual, acoustic or bimodal, are presented from any of the 32 available
target locations. The cat's task is to look to the stimuli and to maintain fixation within the acceptance window
surrounding the target for the duration of the stimulus until a reward is delivered. In the sensory probe task,
the cat must continue fixating LED1 while a second probe speaker is turned on in the middle of fixation. The
sensory probe task is used to study the sensory response of cells to the presentation of the probe. By
Research Design & Methods Page 48
2011-04-22 000051
Principallnvestigalor/Program Direclor(Lasl, first, middle): YIN. TOM, C T
appropriate adjustment of the position of LED1 and SPKR, the auditory receptive field of the cell can be
determined.
The saccade task, which is the most commonly used task, also begins with fixation of LED1, followed by
the presentation of a target (visual, auditory, or both; Fig. 13B), the onset of which coincides with the offset
of the fixation event. The cat is required to maintain fixation on LED 1 until it is turned off and then to move
its eyes to the location of the target within a set time window (500-1500 msec) and maintain fixation until it is
turned off. Usually LED 1 is at the center of gaze so we can start the trials with the animal at a consistent
'centered' position, but it can be anywhere there is a speaker/LED combination. To temporally dissociate
the onset of the target and the .signal to make a saccade, we use the delayed saccade task (Fig. 13C). in
which the target (LED 2 or SPKR) is presented some time before the fixation LED 1 is extinguished. This
results in a period during which the fixation LED and the
target are both on (Fig. 13C). The offset of LED 1 is the A. FIXATION (F)
signal to make a saccade.
For all of the tasks shown in Figure 13, the duration of
various events (e.g .• W1-R, W1-L2, and L2-R intervals)
+, LEDI
. EYE MOVEMENT
I \----
are varied from one task type to another and within tasks, SPKR
so that the cat cannot predict how long any particular
event might last. In addition, there is a temporal window Sy
I I
Ll WI R T
(500 msec after target appearance) within which the cat
has to saccade into the acceptance window or the trial is B. SENSORY PROBE (SP)
judged a miss, in which case no reward is delivered, and
a penalty in the form of a time-out period (double the o~ \ I
intertrial time) is administered. 'We monitor the horizontal
and vertical components of the eye position by sampling
LEDI I
SPKR
the output of the AfD converter at 2-msec intervals and ( )
require that the eye position be within a specified spatial
SY
I I I L2I
Ll WI
I
R
I
T
window about the target for the entire period of fixation in
order to obtain the reward. The duration of the intertrial
period varies from cat to cat (4-8 sec) to allow the animal C. SACCADE (S)
enough time to lick the reward from the feeding tube. On
a typical day a good cat will work for 2 or 3 hours for 200-
400 trials. A large number of different task types and
T:J
LED1
,..--_...J/
I L
targets are always mixed in any run so that the cat
cannot anticipate what the next trial will be. We always LED2 ~:,,:::::I
mix a number of fixation trials in with saccades, delayed ~S~PK~R~ __________~O~ __________
saccades or sensory probe tasks so the cat cannot
anticipate that there will be a saccade from the initial SY Ll WI
I I
L2 W2 R T
LED. Generally the cats are trained and tested 5
days/week.
D. DELAYED SACCADE (OS)
Data analyses
The dependent variable of interest is gaze position,
r;J / Ir--......\~__
which in the head-fixed animal is equivalent to eye
LED1
position, evoked by auditory or visual stimuli. To measure
LED2 ~::::::::::~
final eye position we use eye velocity to define the
beginning and end of eye movements as the time at
which fixation ended and restarted. respectively. The
"end of fixation" is the time at which the amplitude of the
eye velocity trace first exceeds 2 SDs of the mean
baseline (Populin and Yin 1998a). The mean baseline is
computed from a 100-130 msec duration of the velocity Fig. 13 Schematic diagrams of the four behavioral tasks.
In each panel are shown from top 10 bottom a typical gaze
trace just prior to the onset of the initial fixation LED, during or eye movement, timing ofthe visual (LED) and acoustic
which time the eye is expected to be stationary. (SPKR) targets and behavioral events.
Conversely. the "return to fixation" is defined as the time at
2011-04-22 000052
which the amplitude of the velocity returned to within 2 SDs of the mean baseline. Final eye position is the
eye position at the time of "return to fixation". Identical steps are followed for the vertical component of eye
position and errors are computed separately for the x and y directions. In trials with corrective eye
movements, the return to fixation is measured at the end of the last corrective movement. These
procedures for defining the end of fixation were developed in our lab and are, we believe, superior to the
usual methods of defining the start and end of the saccade using an absolute eye velocity or percent
movement criterion. The latency of response is given by the time of "end of fixation".
The figures in the Progress Report were chosen to give a sample of the type of analyses that we use.
Fig. 1A shows raw gaze shift movements during the course of single trials, Fig. 1B shows a scatter diagram
of the final gaze positions on an X-Y plot of space and Figs. 1C and 1D show how we quantify separately
for elevation and azimuth the accuracy (slope or gain of the final gaze position vs motor error plot) and
precision (standard deviation of the residual error d) which is a measure of the precision of the responses.
Electrophysiological recordings
After the behavioral training and psychophysical testing is completed, we do a second sterile surgery
under gas anesthetic to implant a recording chamber placed over the area of interest. In the case of the
inferior colliculus, we place one chamber centered on the midline, which allows access to the ICC of both
sides. Extracellularly recorded action potentials from single cells are recorded with tungsten microelectrodes
using standard techniques for amplification, filtering and display. A Narishige hydraulic microdrive moves the
microelectrode under remote control. Spikes from single cells are discriminated with a BAK spike
discriminator and spike times relative to the synchronization of the stimulus are saved in a unit event timer to a
precision of 1 IJsec. Spike times are used to construct on-line post-stimulus time, interval, and period
histograms, dot rasters, as well as measures of spike discharge rate as a function of any input variable. For
recordings in the head-free animal, our Evarts-style microdrive is too bulky so we use a much smaller and
lighter Narishige microdrive.
Averaged brainstem response (ABR)
To get an objective measure of hearing in our cats', we routinely perform an ABR following the
procedures outlined by Shepherd and Clark (1985). The cats are anesthetized with an injection of ketamine
hydrochloride (15-20 mg/kg) and acepromazine (.2 mg/kg), and given atropine methyl nitrate (0.15 mg/kg)
to suppress mucus. This is usually adequate to keep the animals anesthetized for about an hour.
Additional shots of ketamine are administered if the procedure runs longer. The cat is positioned in an
upright position using the head post and a speaker is placed about 10 cm from the ipsilateral pinna. The
contralateral ear is plugged with Otoform. Needle electrodes are inserted subcutaneously into the ipsilateral
and contralateral mastoid with an additional indifferent needle. Responses are recorded differentially and
amplified (10 4 ) and filtered (150 Hz to 3 kHz) using a Krohn-Hite filter. The responses are digitized by
sampling at 10kHz. Clicks are delivered at 20 Hz and averaged 500-1000 times. The amplitude of the
clicks are varied so that the threshold for ABR responses can be determined.
Histology
At the conclusion of each experiment the animal is given a lethal dose of pentobarbital and the brain fixed
by immersion or perfusion through the heart. Two or more pins are placed into the brain on the outer edges of
the areas studied by a special device that references the pins to known locations in the recording cylinder.
The tissue is cut into 50-lJm frozen sections and stained with cresyl violet so that electrode tracks and lesions
made during the course of the experiment can be seen. We reconstruct the positions of all cells studied with
attention to the possibility that cells involved in spatial hearing are differentially distributed within the SC and
ICC and may be arrayed in a spatial map.
Behavioral Controls
The waveforms used to generate the acoustic stimuli are played by a TDT stimulus system. These
signals are fed through mercury relays that select any of the 32 available channels and are connected to 32
audio amplifiers. This arrangement, which allows the background noise of the amplifiers to play
continuously through the speakers, is preferable to one in which a single audio amplifier drives all 32
speakers through the mercury relays, because in the latter case the cats were apparently able to hear a
faint transient when the background noise of the amplifier is switched to a different speaker. Two other
2011-04-22 000053
PrincipallnvesUgalor/Program Director (last, firsl, middle): YIN, TOM, C T
precautions are taken to minimize the possibility that switching transients, rather than controlled acoustic
signals, could provide the cats with information as to which speaker was selected. First, the selection of the
speaker is done shortly after the synchronization pulse that marks the onset of a trial, rather than just before
the acoustic stimulus is turned on, to temporally dissociate the selection artifact from the acoustic signal. .
Second, we select all speakers rapidly in succession followed by deselection of all out the speaker to be
used, thereby producing transients in all channels. These controls were instituted when we discovered that
the cats were still able to do the task, albeit with many errors, when the stimuli were fully attenuated with our
original setup with only one audio amplifier driving 16 speakers. In addition, to lessen the possibility that
differences in speaker characteristics may assist in identifying and localizing individual speakers, we rove
the level of each auditory trial over a 20 dB range in 2 dB steps, above the empirically determined 75%
correct threshold.
Saccades to novel targets Because there are a finite number of possible tar ets and the ViSllalla:t~ :J
are alwa s laced at the center of a s eaker we were concerned tha X 0
~CQoQill'ffi[JQiQlj~'iilliSll:mln;z;~eessoommee;rrlrrmleeiS[===~~-'~ ..---'
and audlto
--¥ ~ rials involving theseltest targets were ran
tar ets located at other positions
om y Interspersed wit tna s to visual
... J.
'-;;Tr.:::l,"==,"",¥==:c:rl.-..lml ar tests Wit nove speakers shifted from their normal posillons were performed in
a 0 our su jects with similar results including tests with the head-free cats.
The combined visual-auditory stimuli used during the first stages of training and the randomly intermixed
vilLual and auditorv trials presented from the same locations durinq testing sessions raise the possibility that·
I ~ Several lines of evidence show that
our ca s were localizinq sound and not resoonding from memory. First/ \
Reward contingencies.
The cats are required to look at visual or auditory targets by maintaining eye position within a square
electronic acceptance window centered on the target. Once the eye enters the window, the fixation time for
the target is started, and the eye has to remain within the window or else the trial is terminated with a time-
out. Because of differences in the accuracy with which visual and acoustic targets are localized, the
windows are of different sizes; for visual targets the window was 2_5°, and for broad-band auditory targets
the window was 6-12° (see below).
The size of the acceptance window in any behavioral task is determined by balancing two conflicting
considerations. To obtain optimal behavioral performance from the cat, the window should be small so that
the cat cannot relax and be rewarded for lackadaisical work. On the other hand, we want the cat to tell us by
its eye movements where it heard the sound, not where it learned to get a reward. Ideally then, the window
should be large enough to encompass all diligent attempts to look at the target but small enough to prevent
half-hearted attempts at being rewarded. There is no way of knowing with our preparation whether
inaccurate saccades were attributable to inattentiveness or to mislocalization. This is an inherent limitation
of this paradigm. Adding to this difficulty is that the behavioral tasks differ in their difficulty, as judged by
human observers, and that the cats' motivational level varied, as judged by how eagerly they approached
the tasks of the day. The acceptance window is only used during the experiment to determine whether to
deliver a reward and does not affect the estimates of localization, because the final analysis includes both
successful and unsuccessful trials.
2011-04-22 000054
Princlpallnvestigator/Program Director (last, first, middle): YIN, TOM, C T
Eye coil calibration

The eye coil is calibrated with a behavioral procedure that relies on the natural instinct of the cat to look
at a small light source that suddenly appears in the visual field. This is a fundamental assumption that is
made by virtually everyone in the oculomotor field. Adjustments are made to the polarity of the horizontal
and vertical channels to match the actual direction of the cat's eye movements. The output of the coil
system is recorded when the cat's eye assumes a stationary position at the end of eye movements evoked
by visual stimuli presented from known positions. The vertical and horizontal components of eye position
are fit separately with linear equations. The coefficients obtained from the fitting procedure are used by the
data collection and analysis software to convert the voltage output of the coil system to degrees of visual
angle. Small corrections are made in the coefficients as the cat begins to learn the task and fixate targets
more accurately.
Head coil calibration
Several different techniques have been used in the literature to calibrate the head coil of unrestrained
animals. Freedman and Sparks ('97) manually moved the head of the monkey through known angles while
Guitton et al. ('90) oscillated the field coils about the cat while its head was fixed. Our procedure makes use
the cat's own head movements. One problem with calibrating the head coil with unrestrained heads is
estimating the pitch angle of the head, which affects the calibration. To estimate the pitch of the head a
small laser pOinter was mounted on the cat's headpost, the pitch and yaw of which could be precisely
adjusted. The laser's power supply could be gated on and off by the 'reward' signal that the computer sent
to the peristaltic pump. When the cat made a 'correct' saccade, the laser pOinter would illuminate briefly a
point on the black translucent cloth in front of the speakers. While the cat worked on the visual fixation task,
we monitored via closed-circuit infrared camera where the laser pointed. For trials where the LED was at
(0°,0°), adjustments were made in the position of the laser pointer until, on average, the laser pointed
directly at the LED that was illuminated, thus giving us the position that the cat held its head during these
tasks relative to the laser pointer. We then immediately calibrated the head coil by manually moving the
cat's head so that the laser pointed to the LEDs corresponding to the desired location. At each location, we
sampled the voltage from the coil. A linear equation was fit to the voltage-location function, separately for
horizontal and vertical, and the coefficients of the fits were used to compute head orientation from the x-y
voltages. Control experiments with a dummy coil indicate that the presence of the experimenter does not
alter the calibration.
Pinna coil calibration
The calibration of the pinna coils is more problematic than for the eye and head coils since the
positioning of the coil behind the ear and the cat's own ear position when it is fixating a target are both
somewhat arbitrary. We make use of our observation that cats will adopt a reliable and consistent "ready"
position while awaiting the onset of the initial target, usually at the position straight ahead (Populin and Yin,
1998b). However, we have found that different cats adopt different ready positions, some with the ear
upright while others less so. When surgically implanting the coil behind the ear, we attempt to position it so
that the coil is as close as possible to be perpendicular to the field coil magnetic field vector. To do this we
either tape a dummy coil behind the ear while the cat is working if it has previously had eye coils implanted
or we stand behind the cat while it is working and mark the likely spot on the pinna where it is the most
upright. Pinna coils are 6 turns of 10 mm diameter of fine Teflon-coated stainless steel wire (Alan Baird).
The calibration of the coil on the ear entails estimating the angle of the coil while the cat is in the "ready"
position, measuring the yaw and pitch angles of that position with a device allowing a pair of protractors,
and then placing an identical dummy coil at that angle and rotating it through known angles of yaw and pitch
to obtain estimates of the horizontal and vertical components of pinna rotation. We recognize that our
estimate of pinna angle is much less secure than our measurements of eye and head angle since the pinna
has many more degrees of freedom than just pure rotation. It can, for example, translate and distort in
shape as well as rotate in yaw and pitch. Nonetheless, we believe our measurements of pinna position are
superior to that of any other investigators who have tried to do the same thing (Stein and Clamman, 1981,
Young et al. 1996, Hartline et al. 1995, Peck et aI., 1995).
Specific aim I: the neural correlate of orienting of the head, eyes and ears to sound
2011-04-22 000055
Principallnvestigator/Program Director (Last, firsl, middle): YIN, TOM, C T
m coolin
_~~~I:"'IllL"""""'IiII examine·
nd speclfli:c=al"'m:;-.=~wmlrs"'t"'U=r--"~~~~------~~ hese two
-,;e"'x"pe"'r"'lmo;:e"'n"tah-;p;;;:r~oc;;;e;;:dr.:u:r·es are complementary.
Ideally t ese two proce ures WI e one in the same animal
so that the cat serves as its own control. However, until we have more experience with the implantation and
maintenance of the cryoloops, we will first implant a cat with loops that cool AI and PAF and another in
which the SC is inactivated. If these go well, then we will implant cortical cryoloops on one side and an SC
loop on the other side of a cat. On any given day we will cool either the cortex or the midbrain but not both
in that cat. We will begin by studying the effects of cooling in the head free cat because this is the normal
way in which cats operate. Ideally the day will begin with a set of control trials with no cooling followed by
100-200 trials with the cooling probe activated. If the animal continues to work, we will turn off the cooling,
let the tissue return to normal which takes only a few minutes, and run another set of control trials. The
ability to quickly inactivate and activate is the big advantage of using the cryoloop technology. Commonly
our cats may have response biases, orienting one direction or another so the ability to quickly run control
trials is a big advantage. Analysis will focus on the accuracy and preCision of saccades and gaze shifts
made to acoustic and visual targets as well as their latency. Many stUdies show that the deficit following
cortical or SC lesions or inactivation is limited to stimuli from the contralateral auditory space so cooling one
side should be effective.
For aim .Ib ideally we would also study the effects of cooling the IC. However, we have chosen not to
. propose this experiment for two reasons: one, access to the IC is problematic in the cat since it typically is
bisected by the thin bony tentorium so its surface is difficult to expose in a chronic animal, and two, since
the IC is in the pathway for both the midbrain and cortical circuit, IC cooling would not distinguish the two.
In our many acute experiments exposing the IC, we have found that in a small number of cats the tentorium
is further caudal than normal so the much of the surface of the IC is exposed. If we fortuitously have a cat
like that, we would also try cooling the IC to ensure that we get the expected orienting deficit.
Specific aim Ic will examin~-
luata Trom sucn

iliusolYstlmull are olTlicult to coliect since
ered with such low orooaol'lly. If our hypothesis that
,j /.
~.~~__~~~~~~~~~1CC~ ____________~ ______~~~~~ )hen we medict that __~)
Potential difficulties in specific aim I

Our hypothesis in aim la and Ib is that} ~
[ L _ - -_ _ _-----O)IThis proves to be ~e case, we would stili neeo'""'t"'o...,s"'h-=o.,.,w"t:i:"ha=<tr - - - - -
2011-04-22 000056
e Ian to demonstrate this in two ways: one}
Cit K \ "everal experiments from th how that uni ateral

\""-o""n=s-;:or::co~rt;:;;i;::c:::-alC:r::::e::gr:io:-:n=s-'AIT-:a"'nCTI~;;'!:p==ro~d:;:u:-::ce a dramatic and complete loss of ability to approach sound
sources in the contralateral sound field. If our cooling is effective, we should see the same behavioral deficit
if our cryoloops are working.
Another potential difficulty in interpreting the results of these inactivation experiments stems from the
presence of a prominent, but little understood, corticofugal projection (Winer etal., 1998; Winer, 2005) from
the auditory cortex to the IC. Outside of an extensive series of studies in the echolocating bat (see review
Suga et aI., 2000), little is known about the role of the corticofugal system in modulating IC activity.
Stimulation of AI can evoke inhibitory effects in about half the cel s in IC of the rat Mitani et
~iPel:r~984). Even if, as we hypothesize,'
. is likely thaC ,)1.(" -
ow the absence of that modulation when the cortex is cooled will be reflected in the o[len~
lor 0 t e cat is not known and is difficult to predict. The cryoloops and their associated pumps will
introduce some ferromagnetic material into the space around the cat. This has the potential of distorting the
magnetic search coil system. Therefore we will always run the cat with the cryoloops and all the gear in
place but without cooling at the beginning of each session so we have a control for such distortions.
Specific aim II: the vestibulo-auricular reflex (VAR)
Our procedures for surgically implanting pinna coils on the ears, calibrating them, and analyzing the
pinna movements are well described in our previous publications and outlined above. We routinely implant
both ears when we do the surgery in implanting eye coils.
Inactivation of the semicircular canals In s ecific aim lIa we have h othesized t a(".><\' -
::JI( hich we call the
VAR, is mediated b We have noted similarities in the time course and
action of the VAR with the VOR, which stabl izes the retinal images in the presence of head movement and
shown that the VAR is present for passive head movements which eliminates the possibility that it arises
from an efference copy of th1l..hea rl movement sign To definitivel show that the ori in of the VAR is
vestibular it is necessa t
2011-04-22 000057
Principallnvestigalor/Program Director (Last, firsl, middle): YIN, TOM, C T
We will do the vestibular plugging surgery in a cat that has been thoroughly tested for the active and
passive VAR. Both active and passive VAR can be conveniently studied in trials in which the cat is given an
acoustic target in the periphery, which triggers orientation to the target, and rotation of the platform during
the fixation of that target (Fig. 10). The initial orientation elicits an active VAR and the subsequent platform
rotation elicits a passive VAR. The platform can be rotated at 60-90o/sec and is initiated at a random time
during the fixation of the acoustic target. Canal plugging in squirrel monkeys is more effective at low
frequencies (2-4 Hz) than high (Lasker et aI., 1999). Frequency spectra of our head movements show that
most of the power is below 2 Hz but there is significant power up to about 5 Hz. Thus, canal plugging may
not affect the highest frequencies components of the head movement. As discussed in the Progress
Report, we have found that cats differ considerably in the extent to which they show a vestibulo-colic or
cervico-colic reflex, i.e. the propensity to turn their heads' when the body is rotated on the platform in order
to compensate for platform rotation. Of course the presence of the reflex negates the platform rotation so
we cannot use trials in which the head does not rotate with the platform.
We compute the gain of the VAR using methods that have been developed in studies of the VOR
(Huterer and Cullen, 2002). For active head turns we compute the velocity of head and ear-on-head
movement and use the ratio of the peak ear-on-head velocity to peak head velocity to express the VAR.
Usually the head and ear velocity signals have well-defined peaks usually with the peak head velocity
leading by about 10 msec. For the passive movements, the velocity profiles are broader with rio well-
defined peak so we have used the ratio of mean ear-on-head velocity to mean head velocity during the
passive head rotation (Tollin et al., 2009). Since we are also monitoring gaze in all of these measurements,
we can compare the VOR and VAR gain changes following canal plugging.
In Aim lib we will stUD
. trtmt s ort msec and long duration 1 sec

before a nd after canal pluggi ng will b 'F~-,-,-=,,-,,==.c""7::,-,==-=='-'-''''--'=='-''-''''-'=~='=''-
k \h addition to stud in ther-'-------·--:-;(:?-
attention to the
head restrained:r."S-;;:in;;;c:;:;e--;:w;;;e:;O:;;;;;err;le:;;v;;;e;-;t~ar-fl'''eCU=h'helps to stabilize auditory space in the face of head
movements, we would expect to see deficits when the cat is working with the head free but not when
working with the head fixed.
Aim IIc will examine a hitherto unexplored aspect of the VAR in normal cats, namely whetheR"~
V \ThiS aim should be straight forward though we are not set up
fo proVide passive rotati'On in the pitch plane so we will only be able to test the active VAR. .
Potential difficulties in specific aim /I
Specific aim III: studies of motor control of the pinna

Aim ilia will compare the motor control of the pinna with the well-studied oculomotor system. We will
begin by recording from motoneurons in the facial nucleus that innervate the pinna muscles in our awake
cats while they work on the localization task. Initially, while learning the physiological 'topography' of this
region of the brainstem, we will record while the head is restrained simply because recording is much easier
than when the head is free to move. The facial nucleus is accessible from a dorsal approach by traversing
through the cerebellum behind the tentorium. The superior oliv ry nuclei and abducens nuclei nearby will
hel= to guide us in finding the faciaU:uicleus...W.e.a . . ate that' X ~
( - - ----1
2011-04-22 000058
PrincipallnvestigatorJProgram Director (last, first, middle): YIN, TOM, C T
. ~11DWiI1 test lor tner·~------,/(---:K=----------------- ~

~
Aim Illc will examine the role of pinna movements on the localization behavior of the cat. For this aim
the pinna muscles will be denervated bilaterally by cutting the branches of the auriculoposterior and
auricularis externus divisions of the facial nerve as well as the temporal branch of the temprorozygomatic
division of the faCial nerve (Vidal et aI., 1988). We have done this procedure as part of an earlier study in
which we were studying the modulation of SC auditory neurons by eye position and wanted to ensure that
the modulation was not due to changes in ear position (Populin et aI., 2004). Following pinna denervation,
we will test the accuracy and precision of localization as well as monitor latencies of the head, eye and ear
while the cat works with the head free. Since the pinna serves to selectively amplify sound from a particular
direction, it will be important in this experiment to include relatively low level sounds. It could very well be
that the main job of the mobile pinna is to amplify the sound. If we test at high sound levels, this advantage
may not be needed.
Potential difficulties in specific aim 11/
The success of aim ilia will hinge on our ability tel ~ ~ince
there are many more muscles that innervate the pinna than there are 10The eye, the difficulty may be just
finding the right area ofthe facial nucleus that contains motoneurons that move the ear laterally and
medially, the two azimuthal directions we will explore. The motoneurons are large and aggregated together,
we don't anticipate any special difficulty. Finding the paralemniscal zone in the midbrain will be more
problematic because of the small size of the nucleus and smaller neurons. Fortunately for us, the cat's bony
tentorium, which is a barrier for microelectrodes, lies between these two targets so it should not be a
problem. In the past when we have recorded from the IC, which sits directly below the tentorium, we have
first surveyed the cats using MRI to pick out those whose tentorium is more caudal, allowing the IC to be
accessed from the dorsal surface.
For aim IIlb we will rely on recordings from aim ilia to estimatef
)Keller and .
k.,..,., t,-u-;d~ie--,d,..,trh-e-,s-'a""'"m'"'e-p"-r'-'o"b"le""m""-"'in"""-ab;:-dTu-c-e-n"""s-m=ot-:-o-n-e-u-ro-n-s-,-'sh"""o:-w-e-d-'--v;Cirt;-u-::aTollv:-'no r.h'mne
R(0-.:b-,.in:-s-o-::n-(;::;1-,;9"'7""8,...),..,.w,,;h:-o-s.... in
the discharge following forced ductions of the eye. If the responses are the same irV 1
there will be no problems in interpreting the responses. However, if we get a latency longer than predicted
from the efferent latency, then the interpretation of the results may be more problematic.
In aim IIIc in which we will denervate the pinna muscles, one problem is reinnervation of the muscles by
the cut nerve over a period of a few weeks. We have experienced this reinnervation in our studies of the SC
(Populin et aI., 2004). So the post-denervation localization tests must be done promptly following the
lesions.
Timeline
Aim Year 1 Year 2 Year 3 Year 4 Year 5
la XXXXXXXXXXXXXXXXXXX
Ib
Ic XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
lIa
lib XXXXXXXXXXXXXXX(~~~~~~~~~~
XXXXXXXXXXXXXXlC
IIc XXXXXXXXXXXXXXXX
ilia XXXXXXXXlOOOO:XX:lOOOO<XXOOOO<X
IIIb XXXXXXXXXXXXXXXXXXXXXXXXXXX
IIIc XXXXXXXXXXXXXXXXXXXXXXXXXXXX
2011-04-22 000059
E. 8) PROGRESS REPORT PUBLICATION LIST
Papers published since last renewal of grant DC07177 submitted 312004

Batra, R. and Yin, T.C.T. Cross-correlation by neurons in the medial superior olive: a re-examination. J.
Assoc. Research Otolaryngol. 5: 238-252, 2004.
Dent, M.L., Tollin, D.J., and Yin, T.C.T. Gats exhibit the Franssen effect illusion. J. Acoust. Soc.
Amer. 116: 3070-3074, 2004
Yin, T.C.T. Buried in the noise. (invited Editorial Focus) J. Neurophysiol. 91: 1934-1935,2004.
Populin, L.C., Tollin, D.J:, and Yin, T.C.T. Effect of eye pOSition on saccades and neuronal responses to
acoustic stimuli in the superior colliculus of the behaving cat. J Neurophyslol. 92: 2151-2167, 2004.
Tollin, D.J., Populin, L.C., and Yin, T.C.T. Neural correlates of the precedence effect in the inferior
colliculus of behaving cats. J. Neurophyslol. 92: 3286-3297, 2004.
Tollin, D.J., Populin, L.C., Moore, J., Ruhland, J.L., and Yin, T.C.T. Sound localization performance in the
cat: the'effect of restraining the head. J. Neurophysiol. 93: 1223-1234, 2005a. (subject of Editorial
Focus).
Tollin, D.J., Populin, L.C., Moore, J., Ruhland, J.L., and Yin, T.C.T. Response to Letter to Editor ("Heffner,
H.E. and Heffner, R.S. "The sound-localization ability of cats" J. Neurophyslol. 94: 3653-3655, 2005b).
Dent, M.L., Tollin, D.J. and Yin, T.C.T. Psychophysical and physiological studies of the precedence effect
in cats. Acta Acustica 91: 463-470, 2005.
Tollin, D.J. and Yin, T.C.T. Interaural phase and level difference sensitivity in low-frequency neurons in the
lateral superior olive. J. Neurosci. 25: 10648-10657,2005. PMCID: PMC1449742
Joris, P.X. and Yin, T.C.T. A matter of time: internal delays in binaural processing. Trends in Neurosci.
30: 70-78, 2007.
Moore, J.M., Tollin, D.J. and Yin, T.C.T. Can measures of sound localization acuity be related to the
precision of absolute location estimates? Hear. Res. 238: 94-109, 2008. PMCID: PMC2494532
Tollin, D.J., Ruhland, J.L., and Yin, T.C.T. The vestibulo-auricular reflex. J. Neurophysiol. 101: 1258-
1266, 2009. PMC journal - in process
Book Chapters
Tollin, D.J., Dent, M.L. and Yin, T.C.T. Psychophysical and physiological studies of the precedence effect
and echo threshold in the behaving cat, Auditory Signal Processing: Physiology, Psychophysics,
and Models, D. Pressnitzer, A. de Cheveigne, S. McAdams, and L. Collet (Eds.), Springer, NY., pp. 429-
435,2005.
Yin, T.C.T. and May, B.J. Acoustic behavior and midbrain function. In The Inferior Colliculus, JA Winer,
C.E. Schreiner (Eds.) Springer-Verlag, pp. 426-458, 2005.
Tollin, D.J. and Yin, T.C.T. Sound localization: neural mechanisms. In Encyclopedia of Neuroscience,
Volume 9 Larry Squire, (Ed.), Oxford: Academic Press, pp. 137-144,2009.
Yin, T.C.T. Audition. In Neuroscience in Medicine, 3,d edition, P. Michael Conn, Ed. Totowa, N.J.:
Humana Press, pp. 575-589, 2008
(in press).
(in press)
list of Publications Page 57
2011-04-22 000060
Principallnvestigator/Program Director (last. first, middle): YIN, TOM, C T
Abstracts
Dent, M.L., Tollin, D.J., and Yin, T.e.T. The influence of sound source position on free-field measurements
of the precedence effect in cats. Assoc. Res. in Otolaryngol., 27: 816, 2004.
Ruhland, J., Tollin, D.J., and Yin, T.e.T. The effects of stimulus duration, level and spectral content on
sound localization in cats. Assoc. Res. in Otolaryngol., 28: 958, 2005.
Tollin, D.J. and Yin, T.e.T. Low-frequency, interaural-delay sensitive neurons in the lateral superior olive
act as coincidence detectors. Soc. Neurosci. 36: 544.15, 2006.
Ruhland, J.L. and Yin, T.e.T. Localization of pure tones by cats. Assoc. Res. in Otolaryngol. 30: 184, 2007.
Ruhland, J.L. and Yin, T.e.T. Localization of high pass, low pass, and narrow band sounds by cats. Assoc.
Res. Otolaryngol. 31: 586, 2008
Ruhland, J.L. and Yin, T.e.T. Passive rotation of the head elicits the vestibulo-auricular reflex (VAR) in
cats. Soc. Neurosci. 38: 367.21,2008.
List of Publications Page 58
2011-04-22 000061
Principallnvesligator/Program Director (last, first, middle): YIN, TOM. C T
F. VERTEBRATE ANIMALS
1. The overall aim of this project is to understand the neural mechanisms of sound localization. These
results will help us to understand how the brain integrates auditory information from the two ears. This
circuitry plays a major role in our ability to detect signals in the presence of background noise, which is the
major symptom of elderly people with hearing loss. Understanding the neural mechanisms will help in the
design of hearing aids and therapy. Since many of the proposed experiments are behavioral, we cannot
avoid the use of animals for training and testing. We will use the domestic cat (Felis catus). About 5 adult or
juvenile, domestic cats of either sex with clean external and middle ears will be used in each year of these
studies. We prefer young animals who are physically nearly adult in size. We buy the cats from commercial
breeders. The experiments involve extensive training, testing, and recording so that each animal becomes
extremely valuable. It is common for us to have cats in the lab for over a year, sometimes as long as 3-4
years.
2. The cat is an ideal animal for our studies. It is naturally a nocturnal predator so its auditory system is highly
developed for locating prey in darkness. More is known about the cat's central nervous system and auditory
system than of any other animal. It is ideal for our studies because it is friendly, smart, can be taught the
behavioral task, and plentiful. Its auditory system is well developed and similar to that of the human, and for
the purposes of this application it is essential that it has a mobile pinna. We use small numbers of animals
because each cat undergoes extensive training.
3. Veterinary care is provided by the Animal Care facility of the Medical School, operating under the auspices
of the Research Animal Resources Center (RARC) which oversees all animal experimentation at the Univ. of
Wisconsin and approves all of our procedures. We are especially dependent on excellent veterinary care
since the health of the animal is paramount. Our experiments depend on the cat cooperating so we have to
ensure that it is not suffering and eager to work. Before we do anything with an animal, we will bring it down
to the lab every day to feed it and get it accustomed to the environment and handlers. We allow the cats free
rein in the laboratory so they get a positive experience from being in the lab compared to sitting in their home
cages all day. The cats are motivated to work because they are food-deprived in their home cages and work
for food reward under standard operant conditioning.
4. This experimental procedure requires multiple surgeries. For its success it is also imperative that the cats
be healthy and comfortable without suffering pain. Therefore, we go to great lengths to ensure that any
potential pain is minimized. Sterile surgeries are done under isoflurane inhalant anesthesia under the
guidance of Animal Care Technicians and Veterinarians from the Research Animal Research Committee
(RARC). Cats are given an initial does of ketamine hydrochloride (20 mg/kg, 1M) and Acepromazine (0.2
mg/kg) in order to insert the endotracheal tube and IV line. Surgeries generally take 4-6 hours. Post-operative
care is a special concern. Immediately after the surgery is completed, the inhalant and endotracheal tube
are removed. The cat is then closely monitored usually by cradling in our hands immediately until they are
recumbent and then placed under a heat lamp during the overnight postsurgical period. We check it
periodically during the night and turn it from side to side to prevent the buildup of fluid in the lungs.
Penicillin (.1 mlllb, s.q.) is given 12 day prior to surgery and 7 days post-surgery. During surgery we
administer fluids (lactated Ringer's) to prevent dehydration, topical analgesics (Lidocaine) to the wound
margins and Bacitracin ophthalmic ointment to the eyes. A prophylactic painkiller (ketoprofen, 2 mg/kg s.q.)
is given for 3 days post-surgery. After the cat has recovered from the surgery, we begin training and testing
in the experimental setup.
5. All cats are euthanised by an IV overdose (100-150 mg) of sodium pentobarbital as recommended by
the Panel on Euthanasia of the American Veterinarian Medical Association.
V.ertebrate Animals Page 59
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Principallnvesligator/Program Director (Last, first, middle): YIN. TOM, C T
E. a) References Cited
Aitkin LM, Phillips SC (1984) Is the inferior colliculus an obligatory relay in the cat auditory system?
Neurosci Lett 44:259-64.
Barbour DL, Wang X (2003) Auditory cortical responses elicited in awake primates by random spectrum
stimuli. J Neurosci 23:7194-206.
Batra R, Kuwada S, Fitzpatrick DC (1997) Sensitivity to interaural temporal disparities of low- and high-
frequency neurons in the superior olivary complex. II. Coincidence detection. J Neurophysiol 78:1237-47.
Batra R, Yin TC (2004) Cross correlation by neurons of the medial superior olive: a reexamination. J Assoc
Res Otolaryngol 5:238-52. . . '.
Beckius GE, Batra R, Oliver DL (1999) Axons from anteroventral cochlear nucleus that terminate in medial
superior olive of cat: observations related to delay lines. J Neurosci 19:3146-61.
Beitel RE, Kaas JH (1993) Effects of bilateral and unilateral ablation of auditory cortex in cats on the
unconditioned head orienting response to acoustic stimuli. J NeurophysioI70:351-69. .
Bendor D, Wang X (2005) The neuronal representation of pitch in primate auditory cortex. Nature 436:1161-
5.
Bendor D, Wang X (2008) Neural response properties of primary, rostral, and rostrotemporal core fields in
. the auditory cortex of marmoset monkeys. J Neurophysiol 100:888-906.
Benson DA, Hienz RD (1978) Single-unit activity in the auditory cortex of monkeys selectively attending left
vs. right ear stimuli. Brain Res 159:307-20.
Benson DA, Hienz RD, Goldstein MH Jr (1981) Single-unit activity in the auditory cortex of monkeys actively
localizing sound sources: spatial tuning and behavioral dependency. Brain Res 219:249-67.
Bizzi E, Kalil RE, Tagliasco V (1971) Eye-Head Coordination in Monkeys: Evidence for Centrally Patterned
Organization. Science 173:452-454.
Blakemore C, Donaghy M (1980) Co-ordination of head and eyes in the gaze changing behaviour of cats. J
Physiol 300:317-35.
Blauert J (1983) In: Spatial Hearing. The Psychophysics of Human Sound Localization pp 1-427.
Cambridge, MA: The MIT Press.
Boudreau JC, Tsuchitani C (1970) Cat superior olive s-segment cell discharge to tonal stimulation. In:
Contributions to Sensory Physiology New York: Academic.
Brand A, Behrend 0, Marquardt T, McAlpine D, Grothe B (2002) Precise inhibition is essential for
microsecond interaural time difference coding. Nature 417:543-7.
Bremen P, Van der Willigen RF, Van Opstal AJ (2007) Applying double magnetic induction to measure two-
dimensional head-unrestrained gaze shifts in human subjects. J Neurophysiol 98:3759-69.
Brugge JF, Reale RA, Hind JE, Chan JC, Musicant AD, Poon PW (1994) Simulation of free-field sound
sources and its application to studies of cortical mechanisms of sound localization in the cat. Hear Res
73:67-84.
Brugge JF, ~eale RA, Hind JE (1996) The structure of spatial receptive fields of neurons in primary auditory
cortex of the cat. J Neurosci 16:4420-37.
Calford MB, Pettigrew JD (1984) Frequency dependence of directional amplification at the cat's pinna. Hear
Res 14:13-9.
Cant NB (2005) Projections from cochlear nucleus to inferior colliculus. In: The Inferior Colli cui us (JA
Winer, C.E. Schreiner, eds), pp 115-131. N.Y.: Springer.
Clarey JC, Barone P, Imig TJ (1994) Functional organization of sound direction and sound pressure level in
primary auditory cortex of the cat. J Neurophysiol 72:2383-405.
Crouch JE (1969) Text-Atlas of Cat Anatomy. Philadelphia: Lea and Febiger.
Crow G, RupertA, Moushegian G (1978) Phase locking in monaural and binaural medullary neurons:
implications for binaural phenomena. J. Acoust. Soc. Am. 64:493-501.
Dent ML, Tollin DJ, Yin TC (2004) Cats exhibit the Franssen Effect illusion. J Acoust Soc Am 116:3070-4.
Dent ML, Tollin DJ, Yin TCT (2005) Psychophysical and physiological investigations of the precedence
effect in cats. Acta Acustica91: 463-470.
Dent ML, Tollin DJ, Yin TCT (2005) Psychophysical and physiological investigations of the precedence
effect in cats. Acta Acustica91: 463-470.
{ (submitted). ]
References Cited Page 60
2011-04-22 000063
Principallnvestigator/Program Direclor (Lasl, first, middle): YIN. TOM, C T
Fitzpatrick DC, Kuwada S, Batra R, Trahiotis C (1995) Neural responses to simple simulated echoes in the
auditory brain stem of the unanesthetized rabbit. J Neurophysiol 74:2469-86.
Folkins JW, Larson CR (1978) In search of a tonic vibration reflex in the human lip. Brain Res 151:409-12.
Freedman EG, Sparks DL (1997) Eye-head coordination during head-unrestrained gaze shifts in rhesus
monkeys. J Neurophysiol 77:2328-48.
Frens MA, Van Opstal AJ (1995) A quantitative study of auditory-evoked saccadic eye movements in two
dimensions. Exp Brain Res 107:103-17.
Frens MA, Van Opstal AJ, Van der Willigen RF (1995) Spatial and temporal factors determine auditory-
visual interactions in human saccadic eye movements. Percept Psychophys 57:802-16.
Fritz J, Elhilali M, Shamma S (2005) Active listening: task-dependent plasticity of spectrotemporal receptive
fields in primary auditory cortex. Hear Res 206:159-76.
Fritz JB, Elhilali M, Shamma SA (2007) Adaptive changes in cortical receptive fields induced by attention to
complex sounds. J Neurophysiol 98:2337-46.
Fuchs A, Robinson 0 (1966) A method for measuring horizontal and vertical eye movements chronically in
the monkey. J. Appl. Physiol. 21 :1068-1070.
Goldberg JM, Brown PB (1969) Response of binaural neurons of dog superior olivary complex to dichotic
tonal stimuli: some physiological mechanisms of sound localization. J Neurophysiol. 32:613-636.
Goossens HH, Van Opstal AJ (1997) Human eye-head coordination in two dimensions under different
sensorimotor conditions. Exp Brain Res 114:542-60. .
Goossens HH, van Opstal AJ (1999) Influence of head position on the spatial representation of acoustic
targets. J Neurophysiol 81 :2720-36.
Gordon B (1973) Receptive fields in deep layers of cat superior colliculus. J NeurophysioI36:157-78.
Guinan JJr, Guinan S, Norris B (1972) Single auditory units in the superior olivary complex. I: Responses to
sounds and classifications based on physiological properties. Int. J. Neurosci. 4:101-120.
Guitton D, Munoz DP (1991) Control of orienting gaze shifts by the tectoreticulospinal system in the head-
free cat. I. Identification, localization, and effects of behavior on sensory responses. J Neurophysiol
66: 1605-23.
Guillon D, Douglas RM, Volle M (1984) Eye-head coordination in cats. J NeurophysioI52:1030-50.
Gultton D, Munoz DP, Galiana HL (1990) Gaze control in the cat: studies and modeling of the coupling
between orienting eye and head movements in different behavioral tasks. J Neurophysiol 64:509-31.
Harris LR (1980) The superior colliculus and movements of the head and eyes in cats. J Physiol 300:367-91.
Harris LR, Blakemore C, Donaghy M (1980) Integration of visual and auditory space in the mammalian
superior colliculus. Nature 288:56-9.
Hartline PH, Vimal RL, King AJ, Kurylo DO, Northmore DP (1995) Effects of eye position on auditory
localization and neural representation of space in superior colliculus of cats. Exp Brain Res 104:402-8.
Heffner HE, Heffner RS (2005) The sound-localization ability of cats. J Neurophysiol 94:3653; author reply
3653-5.
Heffner RS, Heffner HE (1982) Hearing in the elephant (Elephas maxim us): absolute sensitivity, frequency
discrimination, and sound localization. J Comp Physiol Psychol 96:926-44.
Heffner RS, Heffner HE (1988) Sound localization acuity in the cat: effect of azimuth, signal duration, and
test procedure. Hearing Research 36:221-32.
Henkel CK (1981) Afferent sources of a lateral midbrain tegmental zone associated with the pinnae in the
cat as mapped by retrograde transport of horseradish peroxidase. J Comp Neurol 203:213-26.
Henkel CK, Edwards SB (1978) The superior coliiculus control of pinna movements in the cat: possible
anatomical connections. J Comp NeuroI182:763-76.
Hirsch JA, Chan JC, Yin TC (1985) Responses of neurons in the cat's superior colliculus to acoustic stimuli.
I. Monaural and binaural response properties. J Neurophysiol 53:726-45.
Hocherman S, Benson DA, Goldstein MH Jr, Heffner HE, Hienz RD (1976) Evoked unit activity in auditory
cortex of monkeys performing a selective attention task. Brain Res 117:51-68.
Hofman PM, Van Opstal AJ (2002) Bayesian reconstruction of sound localization cues from responses to
random spectra. Bioi Cybern 86:305-16.
Hofman M, Van Opstal J (2003) Binaural weighting of pinna cues in human sound localization. Exp Brain
Res 148:458-70.
Hofman PM, Van Riswick JG, Van Opstal AJ (1998) Relearning sound localization with new ears. Nat
Neurosci 1 :417-21.
2011-04-22 000064
Huang AY, May BJ (1996) Spectral cues for sound localization in cats: effects of frequency domain on
minimum audible angles in the median and horizontal planes. J Acoust Soc Am 100:2341-8.
Huterer M, Cullen KE (2002) Vestibuloocular reflex dynamics during high-frequency and high-acceleration
rotations of the head on body in rhesus monkey. J NeurophysioI88:13-28.
Imig TJ, Irons WA, Samson FR (1990) Single-unit selectivity to azimuthal direction and sound pressure level
of noise bursts in cat high-frequency primary auditory cortex. J Neurophysiol 63:1448-66.
Irvine, D. R. F. The auditory brainstem: processing of spectral and spatial information. 1-277.86. Berlin,
Springer-Verlag.
Jay MF, Sparks DL (1984) Auditory receptive fields in primate superior colliculus shift with changes in eye
position. Nature 309:345-7.
Jay MF, Sparks DL (1987) Sensorimotor integration in the primate superior colliculus. II. Coordinates of
auditory signals. J Neurophysiol 57:35-55.
Jenkins WM, Masterton RB (1982) Sound localization: effects of unilateral lesions in central auditory system.
J NeurophysioI47:987-1016.
Jenkins WM, Merzenich MM (1984) Role of cat primary auditory cortex for sound-localization behavior. J
NeurophysioI52:819-47.
Joris PX, CarneyLH, Smith PH, Yin TCT (1994) Enhancement of neural synchronization in the
anteroventral cochlear nucleus. I. Responses to tones at the characteristic frequency. J Neurophysiol
71:1022-36.
Joris PX, Smith PH, Yin TCT (1998) Coincidence detection in the auditory system: 50 years after Jeffress.
Neuron 21 :1235-8.
Joris PX, Yin TCT (1995) Envelope coding in the lateral superior olive. I. Sensitivity to interaural time
differences. J NeurophysioI73:1043-62.
Joris PX, Yin TCT (1998) Envelope coding in the lateral superior olive. III. Comparison with afferent
pathways. J Neurophysiol 79:253-69.
Joris P, Yin TC (2007) A matter of time: internal delays in binaural processing. Trends Neurosci 30:70-8.
Judge SJ, Richmond BJ, Chu FC (1980) Implantation of magnetic search coils for measurement of eye
position: an improved method. Vision Res 20:535-8.
Kalluri S, Depireux DA, Shamma SA (2008) Perception and cortical neural coding of harmonic fusion in
ferrets. J Acoust SocAm 123:2701-16.
Kanold PO, Young ED (2001) Proprioceptive information from the pinna provides somatosensory input to
cat dorsal cochlear nucleus. J Neurosci 21 :7848-58.
Kavanagh GL, Kelly JB (1987) Contribution of auditory cortex to sound localization by the ferret (MustE;ila
putorius). J NeurophysioI57:1746-66.
Keller EL, Robinson DA (1971) Absence of a stretch reflex in extraocular muscles of the monkey. J
King AJ, Hutchings ME (1987) Spatial response properties of acoustically responsive neurons in the
superior colliculus of the ferret: a map of auditory space. J Neurophysiol 57:596-624.
King AJ, Jiang ZD, Moore DR (1998) Auditory brainstem projections to the ferret superior colliculus:
anatomical contribution to the neural coding of sound azimuth. J Comp Neurol 390:342-65.
Klingon GH, Bontecou DC (1964) Auditory field localization. Trans Am Neurol Assoc 89:210-1.
Knudsen EI, Blasdel GG, Konishi M (1979) Sound localization by the barn owl (Tyto alba) measured with
the search coil technique. J. Compo Physiol. A 133:1-11.
Kume M, Uemura M, Matsuda K, Matsushima R, Mizuno N (1978) Topographical representation of
peripheral branches of the facial nerve within the facial nucleus: a HRP study in the cat. Neurosci. L.
8:5-8.
Lasker DM, Backous DD, Lysakowski A, Davis GL, Minor LB (1999) Horizontal vestibuloocular reflex
evoked by high-acceleration rotations in the squirrel monkey. II. Responses after canal plugging. J
Litovsky RY, Yin TC (1998a) Physiological studies of the precedence effect in the inferior colliculus of the
cat. I. Correlates of psychophysics. J NeurophysioI80:1285-301.
Litovsky RY, Yin TC (1998b) Physiological studies of the precedence effect in the inferior colliculus of the
cat. II. Neural mechanisms. J NeurophysioI80:1302-16.
Lomber SG, Malhotra S (2008) Double dissociation of 'what' and 'where' processing in auditory cortex. Nat
Neurosci 11:609-16.
2011-04-22 000065
Lomber SG, Malhotra S, Hall AJ (2007) Functional specialization in non-primary auditory cortex of the cat:
areal and laminar contributions to sound localization. Hear Res 229:31-45.
Lomber SG, Payne BR, Horel JA (1999) The cryoloop: an adaptable reversible cooling deactivation method'
for behavioral or electrophysiological assessment of neural function: J Neurosci Methods 86:179-94.
Makous JC, Middlebrooks JC (1990) Two-dimensional sound localization by human listeners. J Acoust Soc
Am 87:2188-200.
Malhotra S, Hall AJ, Lomber SG (2004) Cortical control of sound localization in the cat: unilateral cooling
deactivation of 19 cerebral areas. J Neurophysiol 92: 1625-43.
Malhotra S, Lomber SG (2007) Sound localization during homotopic and heterotopic bilateral cooling
deactivation of primary and nonprimary auditory cortical areas in the cat. J Neurophysiol 97:26-43.
May BJ, Huang AY (1996) Sound orientation behavior in cats. I. Localization Cif broadband noise. Journal of
the Acoustical Society of America 100:1059-69.
May PJ, Vidal PP, Baker R (1990) Synaptic organization of tectal-facial pathways in cat. II. Synaptic
potentials following midbrain tegmentum stimulation. J Neurophysiol 64:381-402.
Mays LE, Sparks DL (1980) Dissociation of visual and saccade-related responses in superior colliculus
neurons. J NeurophysioI43:207-32.
Meredith MA, Stein BE (1983) Interactions among converging sensory inputs in the superior colliculus.
Science 221 :389-91.
Meredith MA, Stein BE (1996) Spatial determinants of multisensory integration in cat superior colliculus
neurons. J Neurophysiol 75: 1843-57. '
Meredith MA, Stein BE (1986) Visual, auditory, and somatosensory convergence on cells in superior
colliculus results in multisensory integration. J'Neurophysiol 56:640-62.
Merzenich MM, Brugge JF (1973) Representation of the cochlear partition of the superior temporal plane of
the macaque monkey. Brain Res 50:275-96.
Middlebrooks JC (1992) Narrow-band sound localization related to external ear acoustics. J Acoust Soc Am
92:2607-24.
Middlebrooks JC, Knudsen EI (1984) A neural code for auditory space in the cat's superior colliculus. J
Neurosci 4:2621-34.
Middlebrooks JC, Knudsen EI (1987) Changes in external ear position modify the spatial tuning of auditory
units in the cat's superior colliculus. J NeurophysioI57:672-87.
Middlebrooks JC, Pettigrew JD (1981) Functional classes of neurons in primary auditory cortex of the cat
distinguished by sensitivity to sound location. J Neurosci 1:107-20.
Middlebrooks JC, Xu L, Eddins AC, Green DM (1998) Codes for sound-source location in nontonotopic
auditory cortex. J Neurophysiol 80:863-81.
Mills AW (1958) On the minimum audible angle. Journal of the Acoustical Society of America 30:237-46.
Mitani A, Shimokouchi M, Nomura S (1983) Effects of stimulation of the primary auditory cortex upon
colliculogeniculate neurons in the inferior colliculus of the cat. Neurosci Lett 42:185-9.
Mogdans J, Ostwald J, Schnitzler HU (1988) The role of pinna movement for the localization of vertical and
horizontal obstacles in the greater horseshoe bat, Rhinolopus ferrumequinum. J. Acoust. Soc. Am.
54:1676-1679.
Moore JM, Tollin DJ, Yin TC (2008) Can measures of sound localization acuity be related to the precision of
absolute location estimates? Hear Res 238:94-109.
Morasso P, Bizzi E, Dichgans J (1973) Adjustment of saccade characteristics during head movements. Exp
Brain Res 16:492-500.
Munoz DP, Guitton D (1991) Control of orienting gaze shifts by the tectoreticulospinal system in the head-
free cat. II. Sustained discharges during motor preparation and fixation. J NeurophysioI66:1624-41.
Neilson PD, Andrews G, Guitar BE, Quinn PT (1979) Tonic stretch reflexes in lip, tongue and jaw muscles.
Brain Res 178:311-27.
Nodal FR, Bajo VM, Parsons CH, Schnupp JW, King AJ (2008) Sound localization behavior in ferrets:
comparison of acoustic orientation and approach-to-target responses. Neuroscience 154:397-408.
Nodal FR, Doubell TP, Jiang ZD, Thompson ID, King AJ (2005) Development of the projection from the
nucleus of the brachium of the inferior colliculus to the superior colliculus in the ferret. J Comp Neurol
485:202-17.
Oldfield S, Parker S (1984a) Acuity of sound localisation: a topography of auditory space. I. Normal hearing
conditions. Perception 13:581-600.
2011-04-22 000066
Principallnvestigator/Program Director (last, firs!' middle): YIN, TOM, C T
Oldfield S, Parker S (1984b) Acuity of sound localisation: a topography of auditory space. II. Pinna cues
absent. Perception 13:601-617.
Palmer AR, King AJ (1982) The representation of auditory space in the mammalian superior colliculus. '
Nature 299:248-9.
Parker AJ, Newsome WT. (1998) Sense and the single neuron: probing the physiology of perception. Annu
Rev Neurosci 21 :227-77.
Peck CK, Baro JA, Warder SM (1995) Effects of eye position on saccadic eye movements and on the
neuronal responses to auditory and visual stimuli in cat superior colliculus. Exp Brain Res 103:227-42.
Peck CK, Schlag-Rey M, Schlag J (1980) Visuo-oculomotor properties of cells in the superior colliculus of
the alert cat. J Comp NeuroI194:97-116.
Pecka M, Brand A, Behrend 0, Grothe B (2008) Interaural time difference processing in the mammalian
medial superior olive: the role of glycinergic inhibition. J Neurosci 28:6914-25,
Poppel E (1973) Comment of "Visual system's view of acoustic space". Nature 243:231.
Populin LC, Tollin OJ, Yin.TC (2004) Effect of eye position on saccades and neuronal responses to acoustic
stimuli in the superior colliculus of the behaving cat. J NeurophysioI92:2151-67.
Populin LC, Yin TC (1995) Topographical organization of the motoneuron pools that innervate the muscles
of the pinna of the cat. J Comp Neurol 363:600-614.
Populin LC, Yin TCT (1998a) Behavioral studies of sound localization in the cat. J Neurosci 18:2147-60.
Populin LC, Yin TCT (1998b) Pinna movements of the cat during sound localization. J Neurosci 18:4233-43.
Populin LC, Yin TCT (1999) Kinematics of eye movements of cats to broadband acoustic targets. J
Neurophysiol 82:955-62.
Populin LC, Yin TC (2002) Bimodal interactions in the superior colliculus of the behaving cat. J Neuroscl
22:2826-34.
Rajan R, Aitkin LM, Irvine DR, McKay J (1990a) Azimuthal sensitivity of neurons in primary auditory cortex
of cats. L Types of sensitivity and the effects of variations in stimulus parameters. J Neurophysiol
64:872-87.
Rajan R, Aitkin LM, IrVine DR (1990b) Azimuthal sensitivity of neurons in primary auditory cortex of cats. II.
Organization along frequency-band strips. J Neurophysiol 64:888-902.
Recanzone GH, Makhamra SO, Guard DC (1998) Comparison of relative and absolute sound localization
ability in humans. J Acoust Soc Am 103:1085-97.
Robinson OA (1972) Eye movements evoked by collicular stimulation in the alert monkey. Vision Res
12: 1795-808.
Robinson OA (1970) Oculomotor unit behavior in the monkey. J Neurophysiol 33:393-403.
Rose JE, Gross NB, Geisler CD, Hind JE (1966) Some neural mechanisms in the inferior colliculus of the
cat which may be relevant to localization of a sound source. J NeurophysioI29:288-314.
Roucoux A, Guitton 0, Crommelinck M (1980) Stimulation of the superior colliculus in the alert cat. II. Eye
ead movements evoked when the head is unrestrained. Ex Brain' Res 39:75-85.
(in
prep).
adagopan ,Wang X (2008) Level invariant representation of sounds by popu atlons 0 neurons in primary
. auditory cortex. J Neurosci 28:3415-26.
Sanchez-Long LP, Forster FM (1958) Clinical significance of impairment of sound localization. Neurology
8:119-25.
Schaefer KP, Meyer OL, Schott 0 (1971) Optic and vestibular influences on ear movements. Optokinetic
and vestibular ear nystagmus in rabbits. Brain Behav Evol 4:323-33.
Schiller PH, Stryker M (1972) Single-unit recording and stimulation in superior colliculus of the alert rhesus
monkey. J Neurophysiol 35:915-24.
Schofield BR (2005) Superior olivary complex and lateral lemniscal connections of the auditory midbrain. In:
The Inferior Colliculus (J.A. Winer, C.E. Schreiner, eds), pp 132-154. N.Y.: Springer.
Schuller G, Radtke-Schuller S (1990) Neural control of vocalization in bats: mapping of brainstem areas
with electrical microstimulation eliciting species-specific echolocation calls in the rufous horseshoe bat.
Exp Brain Res 79: 192-206.
Schwarz OW, Tomlinson, RW (1990) Spectral response patterns of auditory cortex neurons to harmonic
complex tones in alert monkey (Macaca mUlatta). J NeurophysioI64:282-98.
2011-04-22 000067
Shaw MD, Baker R (1983) Direct projections from vestibular nuclei to facial nucleus in cats. J Neurophysiol
50:1265-80.
Shepherd RK, Clark GM (1985) Progressive ototoxicity of neomycin monitored using derived brainstem
response audiometry. Hear Res 18:105-10.
Siegel JM, Tomaszewski KS, Wheeler RL (1983) Behavioral organization of reticular formation: studies in
the unrestrained cat. II. Cells related to facial movements. J Neurophysiol 50:717-23.
Siegel JM, Wheeler RL, Breedlove SM, McGinty OJ (1980) Brain stem units related to movements of the
pinna. Brain Res 202:183-8.
Smith AL, Parsons CH, Lanyon RG, Bizley JK, Akerman CJ, Baker GE, Dempster AC, Thompson 10, King
AJ (2004) An investigation of the role of auditory cortex in sound localization using muscimol-releasing
Elvax. Eur J Neurosci 19:3059-72.
Smith PH, Joris PX, Carney LH, Yin TCT (1991) Projections of physiologically characterized globular bushy
cell axons from the cochlear nucleus of the cat. J Comp NeuroI304:387-407.
Smith PH, Joris PX, YinTCT (1993) Projections of physiologically characterized spherical bushy cell axons
from the cochlear nucleus of the cat: evidence for delay lines to the medial superior olive. J Comp
NeuroI331:245-60.
Smith PH, Joris PX, Yin TCT (1998) Anatomy and physiology of principal cells of the medial nucleus of the
trapezoid body (MNTB) of the cat. J NeurophysioI79:3127-42.
Sparks DL (2005) An argument for using ethologically "natural" behaviors as estimates of unobservable
sensory processes. Focus on "Sound localization performance in the cat: the effect of restraining the
head". J NeurophysioI93:1136-7.
Sparks DL (1986) Translation of sensory signals into commands for control of saccadic eye movements:
role of primate superior colliculus. Physiol Rev 66:118-71.
Spitzer MW, Semple MN (1991) Interaural phase coding in auditory midbrain: influence of dynamic stimulus
features. Science 254:721-4.
Stein BE, Clamann HP (1981) Control of pinna movements and sensorimotor register in cat superior
colliculus. Brain Behav EvoI19:180-92.
Stein BE, Magalhaes-Castro B, Kruger L (1976) Relationship between visual and tactile representations in
cat superior colli cui us. J NeurophysioI39:401-19.
Stevens S, Newman E (1936) The localization of actual sources of sound. Amer. J. Psychol. 48:297-306.
Suga N, Gao E, Zhang Y, Ma X, Olsen JF (2000) The corticofugal system for hearing: recent progress. Proc·
Natl Acad Sci USA 97:11807-14.
Sun XD, Jen PH (1987) Pinna position affects the auditory space representation in the inferior colliculus of
the FM bat, Eptesicus fuscus. Hear Res 27:207-19.
Suzuki JI, Cohen B (1964) Head, eye, body and limb movements from semicircular canal nerves. Exp
Neurol 10:393-405.
Syka J, Popelar J (1984) Inferior colliculus in the rat: neuronal responses to stimulation of the auditory
cortex. Neurosci Lett 51 :235-40.
Syka J, Straschill M (1970) Activation of superior colliculus neurons and motor responses after electrical
stimulation of the inferior colliculus. Exp Neurol 28:384-92.
Thompson GC, Masterton RB (1978) Brain stem auditory pathways involved in reflexive head orientation to
sound. J Neurophysiol41 :1183-1202.
(in prep.). .
Tollin OJ, Populin LC, Moore JM, Ruhland JL, Yin TC (2005) Sound-localization performance in the cat: the
effect of restraining the head. J NeurophysioI93:1223-34.
Tollin OJ, Populin LC, Yin TC (2004) Neural correlates of the precedence effect in the inferior colliculus of
behaving cats. J NeurophysioI92:3286-97.
Tollin OJ, Ruhland JL, Yin TC (2009) The vestibulo-auricular reflex. J NeurophysioI101:1258-66.
Tollin OJ, Yin TCT (2002) The coding of spatial location by single units in the lateral superior olive of the cat.
II. The determinants of spatial receptive fields in azimuth. J Neurosci 22:1468-79.
Tollin OJ, Yin TC (2003a) Spectral cues explain illusory elevation effects with stereo sounds in cats. J
Neurophysiol 90:525-30.
2011-04-22 000068
Tollin OJ, Yin TC (2003b) Psychophysical investigation of an auditory spatial illusion in cats: the precedence
effect. J NeurophysioI90:2149-62.
Tollin OJ, Yin TC (2005) Interaural phase and level difference sensitivity in low-frequency neurons in the
lateral superior olive. J Neurosci 25:10648-57.
Tsuchitani C (1977) Functional organization of lateral cell groups of cat superior olivary complex. J
Vaadia E, Benson DA, Hienz RD, Goldstein MH Jr (1986) Unit study of monkey frontal cortex: active
localization of auditory and of visual stimuli. J Neurophysiol 56:934-52.
Vaadia E, Gottlieb Y, Abeles M (1982) Single-unit activity related to sensorimotor association in auditory
cortex of a monkey. J NeurophysioI48:1201-13.
Valentine DE, Sinha SR, Moss CF (2002) Orienting responses and vocalizations produced by
microstimulation in the superior colliculus of the echo locating bat, Eptesicus fuscus. J Comp Physiol A
Neuroethol Sens Neural Behav PhysioI188:89-108.
Vidal PP, May PJ, Baker R (1988) Synaptic organization of the tectal-facial pathways in the cat. I. Synaptic
potentials following collicular stimulation. J Neurophysiol 60:769-97.
Whitfield IC, Cranford J, Ravizza R, Diamond IT (1972) Effects of unilateral ablation of auditory cortex in cat
on complex sound localization. J Neurophysiol 35:718-31.
Wightman F, Kistler 0 (1994) Sound Localization. In: Human Psychophysics pp 155-192. Berlin: Springer-
Verlag.
Winer JA (2005) Three systems of descending projections to the inferior colliculus. In: The Inferior Colliculus
(Winer JA, Schreiner CE, eds), pp 231-247. New York: Springer.
Winer JA, Larue DT, Diehl JJ, Hefti BJ (1998) Auditory cortical projections to the cat inferior colliculus. J
Comp Neurol 400:147-74 .
. Winer JA, Schreiner CE (2005) The central auditory system: a functional analysis. In: The Inferior Colliculus
pp 1-68. N.Y.: Springer.
Wise LZ, Irvine DR (1983) Auditory response properties of neurons in deep layers of cat superior colliculus.
J NeurophysioI49:674-85.
Wurtz RH, Goldberg ME (1972) Activity of superior collicul.us in behaving monkey. 3. Cells discharging
before eye movements. J Neurophysiol 35:575-86.
Yin TCT (1994) Physiological correlates of the precedence effect and summing localization in the inferior
colliculi,ls of the cat. J Neurosci .14:5170-86.
Yin TCT (2002) Neural mechanisms of encoding binaural localization cues in the auditory brainstem. In:
Integrative Functions in the Mammalian Auditory Pathway pp 99-159. Berlin: Springer-Verlag.
Yin TCT, Chan JC (1990) Interaural time sensitivity in medial superior olive of cat. J Neurophysiol 64:465-88.
Yin TCT, Chan JCK, Carney LH (1987) Effects of interaural time delays of noise stimuli on low-frequency
cells in the cat's inferior colliculus. III. Evidence for cross- correlation. J Neurophysiol 58:562-83.
Yin TCT, Kuwada S (1983a) Binaural interaction in low-frequency neurons in inferior colliculus of the cat. II.
Effects of changing rate and direction of interaural phase. J NeurophysioI50:1000-19.
Yin TCT, Kuwada S (1983b) Binaural interaction in low-frequency neurons in inferior colliculus of the cat. III.
Effects of changing frequency. J NeurophysioI50:1020-42.
Young ED, Rice JJ, Tong SC (1996) Effects of pinna position on head-related transfer functions in the cat. J
Acoust Soc Am 99:3064-76.
2011-04-22 000069
Principallnvestigator/Program Director (Last, first middle ~O~M~,~C,-"TL---_ _ _ _ _ _ _ _ _ _ _ _ _ _._ _~
13 February 2009
Professor Tom Yin

Department of Physiology
University of Wisconsin
1300 University Avenue
Madison, Wisconsin 53706
Dear Tom,
This letter will confmn my willingness to collaborate on your grant proposal to the National
Institutes of Health entitled "Behavioral and physiological studies of souud localization in the
cat", This is a very stimulating and creative proposal. I look forward to participating on the
projects investigating the role of auditory cortex in head and movements,
My laboratory has extensive experience with cooling deactivation teclmiques to study the
cortical contributions of head and eye movements to acoustic and visual targets, We will work
together to assemble the necessary equipment for your apparatus and I will travel to Madison to
perfOlm the cooling loop implantations and provide any other assistance that may be required, I
very much look forward to the successful execution of the projects described in your proposal.
n' _,_
[
letters of Support Page 67
-I
2011-04-22 000070
Principallnvesligator/Program Director (Last, first, middle): YIN, TOM, C T
-{-
Professor Tom C.T. Yin

Departtnen t of Physiology
University of Wisconsin Medical School
290 i'vledical Science Bldg.
Madison, \XII 53706
Dear Tom:
Tlus letter confIrms my willingness to collaborate on your NIH RO"' grant application entitled
"Behavioral and physiological studies of sound localization in the cae'. The preprint that you sent ll1e
describing ~lC vestibula-auricular reflex is a velY interesting and exciting new result. I believe that the
appropriate lesion to. conftrtn the vestibular nature of the reflex would be to plug the semicircular
canals. Such a procedure would tnarkcdly attenuate the rotational responses of the canals but does not
disturb cochlear function. It is a procedure with which I have a great deal of experience in hmnans and
in nonhuman primates. It has been performed by others in cats and I am confIdent that I could
perform it in cats as well.
Once you get your grant and have a cat suitably traincd, we c~n plnn for me to COIne to IvJadison to do
the canal plugging on the animal(s). rnl willing to COlne as many tllllCS as it is necessary to prove 01'
disprove the hypothesis, but I suspect we will know the answer with just a few cats. As I t11entionco to
you, canal plugging is vcr)' effective for disabling vestibular function at low frequencies but lugh
frequencies can be intact. It would be vcr)' exciting if canal plugging disabled the passive VAR but left
the active V I\R little affected. I look forward to this collaboration and the successful test of the VI\R.
Sincerelv
letlers of Support Page as
2011-04-22 000071
Principal Investigator/Program Director (last. first, middle): YIN, TOM, C T
PHS 398 Checklist
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" Inventions and Patents: YesD No~
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" Previously Reported: Yes D NoD
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Tracking Number:GRANTIOI94930 Funding Opportunity Number:PA~07·070 Received Date;2009·03-04Tl5:42:32·1)4:00

2011-04-22 000072
Principallnv8stigator/Program Director (last. first. middle): YIN, TOM, C T
OMB Number. 0925·0001

4. * Program Income
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Tracking Number:GRANTlOI94930 Funding Opportunit)' Number:PA-07-070 Received Date:2009-03~04Tl5:42:32-04:00

2011-04-22 000073
ESNAP Report FINAL
OMB No. 0925·0001
Grant Number Total Project Period
5R01DC7177-7 From: 12101/2004 To: 11/30/2014
~IN: Review Group: Requested Budget Period:
AUD From: 1210112010 To: 11/30/2011
Title of Project: Due Date: 10/16/2010

Submitted Dale: 10/05/2010
Behavioral and physiological studies of sound localization
~ Program DlrectorlPrincipal Investigator: Applicant Organization:

TomC.T. Yin UNIVERSITY OF WISCONSIN MADISON
UNIVERSITY OF WISCONSIN UNIVERSITY OF WISCONSIN MADISON
DEPT OF NEUROPHYSIOLOGY 21 N. Park Street, Suite 6401
1300 UNIVERSITY AVE MADISON, WI 537151218
MADISON, WI 53706
Department: PHYSIOLOGY
Phone Number: (608) 262-0368
Fax Number: (608) 265-3500 Major Subdivision: SCHOOL OF MEDICINE AND PUBLIC
Email Address: YIN@PHYSIOLOGYWISC.EDU HEALTH
Administrative Official: Signing Official:
-X
Phone Numt~
* /
Fax Number
Email Addre .
-x. Phone Numb,
Fax Number:
Email Address: 1-
Human Subjects: ® No. tU Yes Vertebrate Animals: tU No ® Yes
Animal Assurance Number: A3368-01
Research Exempt: ® No tU Yes
Inventions and Patents: ® No tU Yes
Exemption No: FWA Number: FWAOOO05399
tU Previously Reported
Phase III Clinical Trial: ® No tCi Yes
tU Not Previously Reported
Program "Income: ® No tU Yes

.
Budget Period Anticipated Amount Source
F&A Changes:
Primary Project/Performance Site Location

Organizational Name: UNIVERSITY OF WISCONSIN MADISON
DUNS: 161202122
Street 1: UNIVERSITY OF WISCONSIN MADISON Street 2: 21 N. Park Street, Suite 6401
City: MADISON "\county: !State: WI

Province: ICountry: UNITED STATES Zip/Postal Code: 537151218
Congressional Districts: WI-02
PHS2590
-*' ~~I ~&~, cvJ> torr\-o.d-4°'rvn~ 1~~~ . Page 1
2011-04-22 000074
ESNAP Report FINAL
Additional ProjecUPerformance Site Location

Organizational Name: The Board of Regents of the UW System
DUNS: 161202122
Street 1: 1300 University Avenue IStreet 2:

City: Madison ICounty: Dane IState: WI
Province: ICountry: UNITED STATES IZip/Postal Code: 53706
ProjecUPerfonn.ance Site Congressional Districts: WI·02
PHS2590 Page 2
2011-04-22 000075
ESNAP Report FINAL
Program Director/Principal Investigator: Grant Number
Tom C.T. Yin SR01DC7177-7
Applicant Organization: Period Covered by this Report:
UNIVERSITY OF WISCONSIN MADISON 12/01/2009 - 11/30/2010
Title of Project:
Behavioral and physiological studies of sound localization
SNAP Questions:
Has there been a change in the other support of Senior/Key Personnel since the last reporting period?
~ No tCl Yes
Justification:
Will there be, in the next budget period, a significant change In the level of effort for the PO/PI or other Senior/Key
Personnel designated on the.Notice of Award from what was approved for this project?
~ No tG Yes
Justification:
Is it anticipated that an estimated unobligated balance (including prior year carryover) will be greater than 25% ofthe
current year's total approved budget?
tG No ® Yes
Justification: We anticipate a balance of more than 25% aftha grant largely because our new post-doc, who was set to arrive
September 1, has been delayed due to visa problems. We also had considerable carryover from the previous year because
we were being especially frugal with the prospect of the competitive renewal and tight funding at NIH and the possibility of
having to request a no-cost extension. We have begun to order parts for a cooling apparatus and a computer to run
experiments.
Changes In Select Agent Research? ~ No to Yes
Changes in Multiple PO/PI Leadership plan? ~ No tG Yes
Change in human embryonic stem cell (hESC) line(s) used? ~ No lfj Yes
Justification:
Human Subject Education Requirement:
Has the Involvement of Human Subjects changed since previous submission? ~ No tG Yes
Has the Involvement of Animal Subjects changed since previous submission? ~ No tG Yes
Publications:
Valid NIHMSIO: Citation 10: Citation Source: Citation Text:
2807232 PubMed Central Tollin OJ, McClaine EM, Yin TC. Short-latency, goal-directed
movements of the pinnae to sounds that produce auditory spatial
illusions. J Neurophysiol. 2010 Jan: 103 (1) :446-S7. PubMed
PHS2590 Page 3
2011-04-22 000076
ESNAP Report FINAL
PMID:19889848; PubMed Central PMCID: PMC2807232.
2724336 PubMed Central Dent ML, Tollin DJ, Yin TC. Influence of sound source location on
the behavior and physiology of the precedence effect in cats. J
Neurophysiol. 2009 Aug; 102 (2) :724-34. PubMed PMID:19439668;
PubMed Central PMCID: PMC2724336.
2666401 PubMed Central Tollin DJ, Ruhland JL, Yin TC. The vestibula-auricular reflex. J
Neurophysiol. 2009 Mar; 101 (3) :1258-66. PubMed
PMID:19129296; PubMed Central PMCID: PMC2666401.
PHS2590 Page 4
2011-04-22 000077
ESNAP Report FINAL
Cover Letter:
File is not uploaded

.
Research Accomplishments:
Other Document File:
Other Support File:
PHS2590 Page 5
2011-04-22 000078
ESNAP Report FINAL
All Personnel Report
Program Director/Principal Investigator: Grant Number
TomC.T. Yin 5R01DC7177-7
Name: Commons 10: Degree(s) Name: r

SSN:
-........,
TomC.T. Yin TOMYIN PHD, BOTH, MOTH Months Devoted
l
I
to Project
Role on Project:
PO/PI
Supplement Support:
00", 1
M
"""] E'.~f!.;\\A'" Sum
Name: Commons 10: Degree(s) Name: SSN:
I
-¥ \ BS XXX.XX- Months Devoted
to Project
Role on Project: Supplement Support: DoB: (MMIYY) Cal '\ Acad Sum
Technician ~df.tt
~
{ ~ I XXX-XX- Months Devoted

to Project
Role on Project: Supplement Support: DoB: (MMIYY)

~Acad Sum
Technician ?o,Rf./~
I ~
XXX-XX- Months Devoted
to Project
Role on Project: Supplement Support: DoB: (MMIYY)

~Acad Sum
Sr. Info. Proc. Cons. '70 ((!{"It

~ J XXX-XX- Months Devoted
Role o~ Project:
Programmer/Analyst
Supplement Support: DoB: (MMIYY) E[l '7~/i
to Project
Acad Sum
PHS2590 Page 6
2011-04-22 000079
Progress Report
a. Specific Aims
There were three general specific aims: one was to test the hypothesis that the neural commands for spatial
orientation to sounds by the head, eyes and ears is at a subcortical level involving the midbrain, and not
cortical structures by reversible cooling of the auditory cortex or superior colliculus; two was to examine the
effect of inactivating the vestibular system on the newly described vestibulo-auricular reflex (VAR); and three
was to study the circuitry that moves the pinna as a model motor system and compare it with the well-known
oculomotor circuil.
b. Studies and results

We have continued our behavioral work on sound localization with more detailed studies of the VAR by
examining the incidence of the VAR in the vertical dimension as well as for small head movements. Our
original discovery of theVAR only described the response to head movements in the azimuthal plane and on
the ipSilateral side for large (>15 deg) head movements. To further analyze the limits of the VAR we have
been testin cats with head movement
e a I p emen Ing a VI ua acoustic environment in the behaving cats. To do this we need to stimulate
the cats via modified head phones but at the same time allow the cats to listen to stimuli delivered in the free
field from speakers. The stimuli delivered through the head phones will be filtered by the cat's head-related
transfer function (HRTF). For each speaker position, there are different left and right ear HRTFs. Since the
cats are trained to localize the stimuli by directing their gain we will be able to test whether the cat hears the
HRTF filtered sounds at the same location predicted by the HRTF used to filter that sound. HRTFs have been
p used to simulate free field sound sources in many studies with animals but there is no behavioral evidence that
the animals localize the sounds as predicted. We are following the general strategy described by Wightman
and Kistler (J. Acousl. Soc. Amer. 85: 858-867,1989) in human subjects but adapting the technique to cats.
r
)
To do this, we make Otoform or Reprosil molds of the cat's ears to manufacture a shell to hold the probe tube
that will deliver the virtual sounds while allowing free field sounds to enter the ear canal. From this mold we
can make a cast of the ear canal (from which future ear molds and ear plugs can be made).
The mold is hollowed out with an opening to the eardrum and a small probe tube will be attached to il. The
cats initially have trouble tolerating the ear mold in their ear canal so some period of adaptation is needed by
having the cats wear it for short times initially and gradually increasing the exposure time. If the cats tolerate
wearing the ear molds during experiments, we may have them wear them for longer periods during the day, to
further acclimate them to wearing the ear molds. We have found that immediately after the ear molds are
placed in the ears, the cat's localization is drastically affected, particularly in the vertical dimension. This is true
for both sounds along the horizontal and vertical meridian. After a period of a few weeks of training the cats to
the new HRTFs by including bimodal (visual and auditory targets) stimUli, the errors in the vertical dimension
are gradually decreased. This shows that cats can learn and adapt to new HRTFs even when they are not
heari l1g them chronicallv.
I
We have also spent considerable effort in writing up papers of previous work. Dent et aI., (2009) examined
the combined behavioral and physiological effects of variations in the locations of the sound sources in the
classical precedence effect (PE). The PE was assessed behaviorally in cats while varying the distance
between the two speakers and then neural correlates of the behavior were found in recordings from cells in the
inferior colliculus in the behaving cal. For both behavior and physiology the echo thresholds were shorter for
speakers that were further apart.
2011-04-22 000080
Tollin et al. (2010) examined the movements of the pinna while cats were tested with stimuli that mimicked
the PE. Pinna movements were similar to the behavioral responses of the cats, which were reflected in eye
movements, in that all three components of the PE were seen: summing localization, 1~lizalion dominance
and echo thresholds.
Three other papers have been completed and have been or are abollt to he submitted for publication. O~
Ir I
L
con))rm~
~ ~~~J
i\ltfle context of the delav . e-lalllous·mode ess (l!:L48kl nlS paper
Two/,
Three,)
tones.
}
c. Significance
We are very excited about our discovery of a VAR that parallels the VOR in vision. The VOR is one of the
most well-known and well-studied physiological phenomenon in the nervous system. It is the basis for a whole
field of study of neuronal plasticity since it is easily adaptable if the relationship between head movement and
~
gaze is disrupted or disturbed, e.g. by wearing prism goggles or magnifying or mini in lasses. On the other
and,! re clear differences between the VAR and VOR: the VAR ac
~---,----_~'>'f:.~_~
." ans
We do not anticipate any big changes in our research plans. We will continue to set up the cortical cooling
project and hope to implant a cryoloop in a cat in the coming year. We will also continue our sound localization·
experiments as well as beginning to tackle specific aim 3 of studying the neuronal Circuitry underlying pinna
movements.
e. Publications
TOLLlN, D.J., RUHLAND, J.L., AND YIN, T.C.T. The vestibulo-auricular reflex. J. Neurophysio/. 101: 1258-
1266, 2009. PMCID: PMC2666401 (previously listed but without PMCID number)
DENT, M.L., TOLLlN, D.J. AND YIN, T.C.T. The influence of sound source location on the behavior and
physiology of the precedence effect in cats. J. Neurophysiol. 102: 724-734, 2009. PMCID: .
PMC2724336
TOLLlN, D.J., MCCLAINE, E.M. AND YIN, T.C.T. Short-latency, goal-directed movements of the pinnae to
sounds that produce auditory spatial illusions. J. Neurophysiol. 103: 446-457, 2010. PMCID:
PMC2807232
Personnel:
"*'
J A new post-doc has been recruited into the labC
oom,""';ooo' modeb" Sb, roM'"

>Ie Js a talented electrophysiologist who has
experience in behavioral and physiological recordings In awake rabbits as well as in vitro slice ex . eriments and
be< ~.D.; th' ',b off . .... - -]
2011-04-22 000081

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Notice of Award

RESEARCH Issue Daie: 11/13/2009

Grant Number: 2R01DC007177-06

Project Title: Behavioral and physiological studies of sound localization

Award e-mailed to: NIH@rsp.wisc.edu

Budget Period: 12/01/2009 -11/30/2010

Dear Business Official:

Additional information follows

AWard Calculation (U.S. Dollars)

Federal Direct Costs $212,500

AMOUNT OF THIS ACTION (FEDERAL SHARE) $312,265

~I TOTALS FOR ALL

Document Number: RbCOo 77B

CAN 2010 2011 2013 2014

NIH Administrative Data:

SECTION 11- PAYMENT/HOTLINE INFORMATION - 2R01DC007117·06

SECTION 111- TERMS AND CONDITIONS - 2R01DC007177·06

(See NIH Home Page at 'http://grants.nlh.gov/grants/policy/awardconditions.htm' for certain

This grant is subject to Streamlined Noncompeting Award Procedures (SNAP).

Treatment of Program Income:

SECTION IV - DC Special Terms and Conditions - 2R01DC007177-06

Grants Management Specialist: Castilla Mcnamara

Program Official: Christopher Platt

INSTITUTION: UNIVERSITY OF WISCONSIN MADISON

Facilities and Year 6 Year 7 Year 8 Year 9 . Year 10

YIN, TOM C.T.

L6?(I~ ~,,+ L 09/01/07-04/0109

R90 DK071515 (Yin PI) 09/30/04-07/31/09' .0 calendar months

'Grant is in no-cost extension until 07/30/10

T90 DK070079 (Yin PI)

Training Program in Clinical Neuroengineering

'Grant is in no-cost extension until 07/30/10

ReportsobmiHed on: 11/051200911:07 AM

IRB Confirmation: No IRS Certification was required

Human Subjects Education: No Human Subjects Education was provided

IACUC Confirmation: 10/2212008

Received: 03/04/2009 FOA: PA07-070 Council: 10/2009

2 R01 OCOO7177-06 Dual: Accession Number: 3145120

IPF: 578503 Organization: UNIVERSITY OF WISCONSIN MADISON

Former Number: Department: PHYSIOLOGY

IRG/SRG: AUO AIDS:N Expedited: N

Subtotal Direct Costs Animals:Y New Investigator: N

Senior/Key Personnel: Organization: Role Category:

TOM YIN The Board of Regents of the UW System PDIPI

Stephen Lomber University Of Western Ontario Other (Specify)-OSC

Lloyd Minor Johns Hopkins University Other (Specify)-OSC

Additions for Review

Other publishedlaccepted 05/1212009

Updated Pages publishedlaccepted 05/1212009

SF 424 (R&R) I 03/04/2009

I National Institutes of Health I TITLE: Research project Grant (Parent ROl)

11 •• DESCRIPTIVE TITLE OF APPLICANT'S PROJECT:

a. YES 0 THIS PREAPPLICATION/APPLICATION WAS MADE

19. Authorized Representatlv~.~-:-:--:---;~_=;~====::::r-~~~~_ _-,

20. Pr.-appllcalion I 1 Add Allaehnient 1 Del"leAliacl1!]1.nll;Vi.wi>.II~Ctll;'enl ·1

Tracking Number:GRANTl0194930 Funding Opportunity Number:PA·07·070 Received Date:2009·03·04T15:42:32·04:OO

424 R&R and PHS·398 Specific

Performance Sites·········· .. ·····•······ .. ··•··•··•.. ······•···· .. ··· ....................................... . 4

Research & Related Other Project Information········································ ..•·• ................... .. 5

Project Summary/Abstract (Description)··································· .... • 6

Public Health Relevance Statement (Narrative attachment)················ ..•·••··••·········•···• 7

Facilities & Other Resources···················· .. ·······•·•···••··• 8

Research & Related Senior/Key Person················································........................ .. 12

I~~t!~Sf:~i~i~\CCUPYillg SOl I Ie 900 itt.