Computa(onal

 neuroscience?  
Neural  prosthe(cs  

Neuromorphic  engineering  

Neural  networks  
Neural  engineering  

Computa(onal  neuroscience  

Quan(ta(ve  neuroscience  

Biofeedback  
Neuroinforma(cs  
Brain  machine  interface  
 Computa(onal  neuroscience  

Personal  defini(on:  Computa*onal  neuroscience  is  a  discipline  that  

employs  algorithms  and  simula*ons  guided  by  mathema*cal  theory  
to   mechanis)cally   understand   brain   func*on   through   the  
development  of  models  that  are  biologically  realis)c.  

•   Computa*onal  neuroscience  is  NOT  an  engineering/technology  discipline!  

•   It  is  a  basic  science  discipline  addressing  ques*ons  in  fundamental  research!  

•    Mathema*cs   and   computa*on   are   used   as   efficient   tools   towards  

understanding  brain  func*on  
 To  what  use,  put  do  you,  these  models?  
Biological  data  is  oEen  messy,  and  ridden  with  redundancy.  
What  are  the  essen*al  features  of  this  data  to  explain  what  
the  neuron’s  func*on  is?  

Put   together   a   model   involving   the   basic   components,   and  

describe   an   observed   phenomenon   or   simulate   neuronal  
func*on.  

Ah!  Descrip(ve  model!  

To  what  use,  put  do  you,  these  models?  

There  are  limits  to  what  can  be  done  with  experiments.    

Derive  abstrac*ons  and  data  from  experiments,  and  build  a  

model.  Using  the  model,  come  up  with  testable  predic(ons  
that  can  be  tested  with  available  biological  techniques.  

Eh!  Predic(ve  model!  

 Broad  u(li(es  
•    Sanity  check!  Experiments  don’t  give  precise  answers  owing  to  nonspecifici*es,  
compensa*ons,   etc.   Put   together   a   model   using   the   basic   biologically   precise  
components,   and   describe   the   phenomenon   in   terms   of   your   hypothesis,   it   is  
proof-­‐of-­‐principle.  

•    Complement!   Experiments   have   limita*ons.   Models   have   limita*ons.   Use   one  

limita*on  to  eliminate  the  other!  

•    Guide!   Experiments   without   an   overall   hypothesis   and   theory   are   blind.  

Theore*cal  and  computa*onal  models  guide  through  the  jungle  of  experiments.  

•    Predict!   Using   mathema*cally   rigorous,   and   biologically   realis*c   models,   come  

up   with   hypothesis   of   what,   how   and   why   a   neuron   should   be   doing   a   certain  
func*on.  Test  it  experimentally!  

•    Loop!  Experiments,  theorize,  model,  predict,  test  experimentally,  feed  data  back  
to  models…  ad  infinitum  
 So,  comp  neuro  is  not  just  input-­‐output  mapping  
You   might   have   precisely   replicated   an   input-­‐output   mapping   using  
your   model,   but   you   have   did   nothing   in   the   computa*onal  
neuroscience   book   if   it   is   does   not   include   biologically   realis(c  
components  or  if  it  is  not  biologically  plausible  

Example:  Depth  Percep(on  

LASER  scanner   Human  eye  

 Reality  check  is  very  important!  
•    Ques(on   to   ask:   Is   my   model   taking   the   basic   understanding   of   the   brain  
forward?  
•    PuVng   together   a   bad   model   is   very   very   easy!   Coming   up   with   a   good   model  
that  takes  the  science  forward  is  difficult  and  requires  a  lot  of  rigor  and  details.  

Theory without experiments is empty.

Experiments without theory are blind.
 Scales!  
Behavior  

Systems  
Just   like   neuroscience   research,   computa*onal  
neuroscience   research   also   proceeds   at   mul*ple  
Networks   scales  

Microcircuits  

A   model   that   spans   mul*ple   scales,   explaining   one   in  

Neurons  
terms   of   other   and   assessing   the   effects   of   changes  
in   one   scale   to   changes   in   another,   is   called   a  
Molecules/Channels  
mul(scale  model  

Genes  
 Disciplines  (to  name  a  few)!  
•   Signal  propaga*on  and  integra*on  in  neurons,  oscilla*ons,  excitability  

•   Development,  dendri*c  arboriza*on,  axonal  pa\erning  and  guidance  

•   Informa*on  representa*on,  encoding  and  decoding  by  neurons  

•   Sensory  processing,  mul*scale  sensory  representa*on,  development  

•   Learning,  memory,  experience-­‐dependence  and  plas*city  

•   Behavior  of  networks,  synchrony,  network  connec*vity  and  func*ons  

•   Stability,  homeostasis,  nonlinear  dynamic  equilibrium,  disease  states  

•   Cogni*on,  discrimina*on,  classifica*on  and  their  impairments  

 What  math  has  been  used  by  neuroscien(sts?!  
Unlike   many   other   biological   disciplines,   neuroscience   is   a   field   where   theory  
and  experiments  have  gone  on  hand  in  hand,  pre\y  effec*vely!  

•   Probabilis*c  models,  Bayesian  inference,  Markov  models,  Poisson  sta*s*cs  

—  Decision  making,    fear  and  reward  learning,  synap*c  transmission,  ion  channel  models,  
neuronal  encoding  and  decoding,  single  molecule  interac*ons,  diffusion,  etc.  

•   Differen*al  equa*ons,  nonlinear  dynamics  

 —  ion  channel  models,  single  neuron  computa*on,  synap*c  plas*city,  oscilla*ons,      
 network  interac*ons,  evolu*on  of  any  phenomenon!  

•   Linear  algebra,  real  and  func*onal  analysis  

 —  representa*on  of  sensory  informa*on,  principal  component  analysis,  independent  
 component  analysis,  overcomplete  basis  for  sound  and  visual  representa*on,  transforms,  
 wavelets,  etc.  

And,  so  on…  

 Where  can  we  learn  more  on  comp  neuro?!  
Books:    

a.  Peter  Dayan  and  L.  F.  Abbo\,  Theore*cal  Neuroscience:  Computa*onal  and  
Mathema*cal  Modeling  of  Neural  Systems,  The  MIT  press,  2005.  
b.  Christof   Koch   and   Idan   Segev   (Eds),   Methods   in   Neuronal   Modeling:   From  
Ions  to  Networks,  The  MIT  press,  second  edi*on,  1998.    
c.  Eric  De  Schu\er  (Ed.),  Computa*onal  modeling  methods  for  neuroscien*sts,  
The  MIT  press,  2009.    
d.  Eugene   Izhikevich,   Dynamical   systems   in   neuroscience:   the   geometry   of  
excitability  and  burs*ng,  The  MIT  press,  2006.    
e.  Kenji   Doya,   Shin   Ishii,   Alexandre   Pouget,   Rajesh   PN   Rao   (Eds),   Bayesian  
Brain:  Probabilis*c  Approaches  to  Neural  Coding,  The  MIT  press,  2007.  

Journals  

  Journal   of   Computa*onal   Neuroscience,   Neural   Computa*on,   PLoS  

 Computa*onal  Biology,  and  all  neuroscience  journals.  
What  are  we  going  to  learn  from  these  lectures?  
Behavior  

Systems  

Networks  
How  to  use  NEURON  to  model  biophysically  
Microcircuits   realis(c  single  neurons  and  their  networks?    

Neurons  

Molecules/Channels  

Genes  
 What  are  we  going  to  learn  from  these  lectures?  
Specifically,  how  to  use  NEURON  for  

 —  Modeling  passive  neurons  

 —  Modeling  ion  channels  

 —  Integra*ng  mul*ple  ion  channels  into  a  mul*compartmental  model  of  

   real  3D  neuronal  reconstruc*ons    

 —  Modeling  calcium  handling  

 —  Modeling  excitatory  and  inhibitory  synapses  

 —  Modeling  networks  of  mul*ple  neurons  

Intui*ve   understanding   of   what   each   ion   channel   does   to   various   neuronal  

proper*es.  
 What  are  we  not  going  to  learn  here?  

Anything  that  NEURON  cannot  do  is  not  covered  here!  

•   It  is  a  large  list!!  

We  are  not  going  to  EVERYTHING  that  NEURON  covers,  either!  

 —  e.g.,  parallelizing  NEURON  will  not  be  covered  

 Is  NEURON  the  only  package  that  can  do  all  this?  
Nope!    

There  is  GENESIS,  which  can  do  similar  kind  of  things.  

There   is   MOOSE,   which   can   do   this   and   more   and   integrate   mul*ple  
simula*on  environments  together.  

Then  why  are  we  learning  NEURON?  

Because   the   instructor   has   used   only   NEURON   (when   not   wri*ng   own  
programs,  that  is!)!    

This  is  the  most  widely  used  package  with  ac*ve  user  support,  and  there  is  an  
online   repository   of   models,   with   those   wri\en   in   this   language   being   the  
highest!  

h\p://senselab.med.yale.edu/senselab/modeldb/  
 Well,  then!  Tell  us  about  NEURON.  
Flexible  and  powerful  simulator  of  neurons  and  networks  with  a  easy  GUI  

Delinks   biological   concerns   from   computa*onal   concerns   so   that   users   can  

think  about  biological  problems  while  wri*ng  code  

You   can   specify   the   model   of   the   neuron   with   various   ion   channels   without  
worrying   about   the   numerical   solu*on   of   the   underlying   differen*al  
equa*ons  

You   can   specify   the   requisite   step   size   and   choose   specific   integra*on  
mechanisms   (Euler,   Crank-­‐Nicholson,   etc.),   and   also   have   an   op*on   of  
variable  step  size  integrators  without  worrying  about  how  it  is  implemented  

Spa*al   discre*za*on   and   integra*on   across   compartments   handled  

seamlessly  in  a  mul*ple  compartmental  model    
 Where  do  I  get  it  from?  

h\p://www.neuron.yale.edu  

Free  soEware  available  for  most  opera*ng  systems  —  Windows,  MacOS,  All  
flavors  of  UNIX.  Source  code  available  for  compila*on  as  well  

Database   of   exis*ng   NEURON   models   (around   250   models   of   various   cells/

networks):  h\p://senselab.med.yale.edu/senselab/modeldb/  

Links  to  tutorials  may  be  found  on  the  main  NEURON  page  as  well.  
 HOC,  MOD  

Neuronal  model  (HOC)  

NEURON  
Mechanisms  (MOD)  
Graphical  user  interface  
Ion  channels,  current  
(GUI)  
injec*on,  etc.  
Screen  shot  of  NEURON  GUI  
We  will  do  the  rest  in  the  next  lecture…  

Theory without experiments is empty.

Experiments without theory are blind.