[NEUROSCIENCE I] November 7, 2013

Introduction to Neuroscience & Neuroembryology Page 1 of 6

Neuron doctrine
the nervous system is made up of individually signalling
elements called neurons which contact each other only at
specialized points of interaction we call the synapses
the basic functional unit of the nervous system is the neuron.
It is an excitable cell specialized to receive stimuli and to
conduct a nerve impulse
Neuron
Three components:
o dendrite receives impulse
o cell body
o axon - transmits the impulse away from the cell
body towards its terminal
From there it will go to the next neuron
SYNAPSE - communication between two
neurons
PATHWAY - a chain of communicating
neurons
Impulse travels from the dendrite to the cell body and then to
the axon
The transmission of impulse in a single neuron is electrical,
while from one neuron to another is chemical by means of
neurotransmitters (secreted from the presynaptic terminal
binding to receptors in the post synaptic terminals)
CNS PNS
Collection of
nerve cell bodies
Nucleus Ganglion
Group of axons Fiber
tracts/Lemniscus/Fasciculus
Peripheral nerve
Location Centrally located (Neuraxis) Peripheral
Function correlation, integration, and
processing of nervous
information
Conduit between
the CNS and the
organ systems of
the body*
Components Brain and spinal cord Peripheral nerves
and their
associated
ganglia,
receptors, and
effectors
*The peripheral nerves can either conduct impulses from the organ
systems to the CNS or the other way around.
Sensory (function) or afferent (direction) from organs to
CNS
Motor or efferent from CNS to organs



PNS
3 types of peripheral nerves:
o cranial nerves associated with cranial ganglia
o spinal nerves associated with spinal ganglia or
Dorsal Root Ganglion
o autonomic nerves (peripheral nerves that course
through cranial and spinal nerves and root to
visceral organs)
Foramen Magnum
Junction of the brain and spinal cord
Spinal Cord
Divided into 31 spinal cord segments (8 CV, 12 TV, 5 LV, 5 SV,
1 C), and thus the 31 pairs of spinal nerves as well
Brain
Cerebral hemisphere
o largest
o divide into right and left hemispheres
o deep inside of which are structures belonging to the
diencephalon as well as the basal nuclei (formerly
known as the basal ganglia).
Brainstem
o Found below the diencephalon
o divided into three in rostrocaudal order:
midbrain
pons
medulla
found immediately above the
foramen magnum
Cerebellum found behind the brainstem

Nervous system starts to form at the 3
rd
week of life.
3
rd
week of life formation of notochord
o Source of inducer substance
Seep into the overlying ectoderm and
stimulate it to thicken and form a
structure called the neural plate -> neural
Calibri Lecture Notes
Arial narrow from powerpoint

INTRODUCTION TO NEUROSCIENCE

NEUROEMBRYOLOGY
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groove, while the lateral structure will be
the neural fold.
The two edges of the neural fold will start
to approximate each other, and then
separate with the overlying ectoderm to
form the neural tube.
Before it separates from the overlying
ectoderm, a portion of the neural folds
will also separate from the surface
ectoderm that will not move with the
neural tube; rather it would position itself
dorsolateral to the neural tube, and will
be called the neural crest.
All these events will constitute the
primary neurulation.
o Defines the long axis of the embryo
o Determines orientation of vertebral column
o Produces cell adhesion molecules so that cells in
the overlying notochord will move as a single unit

Primary neurulation
Formation of the neural tube from neural plate giving rise to the brain
and spinal cord up to lumbar levels
Day 18 day 25
Neural tube primordial of CNS
o Rostral 2/3 gives rise to the brain
o Caudal 1/3 gives rise to the spinal cord up to lumbar
levels
o Caudal eminence gives rise to sacral and coccygeal
segments
Neural crest PNS
o Schwann cells
o Cranial nerve ganglion
o Dorsal root ganglion
o Autonomic ganglion
o Chromaffin cells of Adrenal medulla
o Pia and arachnoid of meninges
o Melanocytes
Induction process
o Proper development of a structure would require
the proper development of the surrounding
structures as well
Neural tube formed in primary neurulation will give rise to
the CNS up to the Lumbar portion only

Secondary neurulation
Formation of sacral and coccygeal segments of cord from caudal
eminence ; from day 20-42
Gives rise to the sacral and coccygeal portions
Several small tubules coalesce in CT matrix and then they
form a mass called te caudal eminence
o Acquire a lumen, and fuse with the neural tube
formed by primary neurulation to form the spinal
cord of coccygeal and sacral segments
It is in the neck region where the neural fold start to
approximate each other and form the neural tube during
primary neurulation. It then proceeds rostrally and caudally
along the length of the embryonic disc.
While it is not totally fused, there will be an opening both
rostrally and caudally.
o Rostral opening - anterior neuropore or rostral
neuropore. This communicates the neural cavity
with the amniotic cavity.
o Caudal opening - Posterior neuropore, which
connects the caudal neural cavity with the amniotic
cavity.
o The rostral opening will close first because the
cervical region/neck is closer to the rostral than to
the caudal part of the body. This occurs at day 23-
24
o The caudal neuropore closes at about day 25-26.
When the anterior neuropore closes, it forms a membrane
called the lamina terminalis.
Normally, both openings should close to form the complete
neural tube rostrally and caudally.

DISORDERS of PRIMARY NEURULATION
ANENCEPHALY
o without brain
o Defective closure of anterior neuropore
o No neural tube in anterior
o Aka Meroanencephaly with some degree of
neural tissue, but to cerebral cortex
o Absence of the skull
o 100% mortality baby will live for at most 1 week
o No extraordinary measures, just comfort, warmth,
and baptism (if catholic.)
SPINA BIFIDA OCCULTA
o Non closure of spines of vertebra
o Tufts of hair at the area
o Minimal defect
SPINA BIFIDA CYSTICA
o With protruding mass of tissue at the area of
nonclosure which can be just a meningocoele
(meningeal tissue) or meningomyelocoele
(meninges + neural tissue)
o Graver defect
o Functional impairment
MYELORACHISCHISIS
o Open neural tube at the back
o High mortality
o Prognosis varies on degree of defect
o Functional impairment
Preventive Measures
o 400 ug of Folic acid daily (one month before
pregnancy up to 12 wks of gestation)


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Disorders of Secondary Neurulation
Termed as Myelodysplasia
o refers to malformation of parts of the neural tube formed
by secondary neurulation
o Site marked with unusual pigmentation, unusual hair
growth, superficial capillaries and prominent dimple

Tethered Cord Syndrome
o Abnormality wherein the conus medullaris and filum
terminale are abnormally fixed to the defective vertebral
column
o Affects the exiting spinal nerves from the cord
o Loss of sensation in legs and feet
o Bladder control problems
o External: unusual tuft of hair, violaceous prominent
capillaries in the area; prominent dimple
o More symptomatic than spina bifida

PRIMARY BRAIN VESICLES
o Occurs during 4th week of life
o During the 5th week, primary brain vesicles will
evolve into secondary brain vesicles
o Mesencephalon most primitive segment of the
brain; retained until the secondary vesicle
o Myelencephalon + Metencephalon +
Mesencephalon = BRAIN STEM
o As the different secondary vesicles are evolving, the
shape and size of the neural cavities change

To fit in the skull, these structures will have to flex or bend
o 1
st
bend/cervical flexure between spinal cord and hind
brain(rhombencephalon)
o Cephalic flexure- between the midbrain (mesencephalon)
and forebrain (prosencephalon )
o Pontine flexure demarcates the myelencephalon from
the metencephalon
o Telencephalic flexure- between the diencephalon and
telencephalon

TRANSVERSE DIFFERENTIATION of PRIMITIVE NEURAL TUBE

Neural tube
o Ventricular zone
o Marginal zone
o Intermediate zone Mantle layer
Alar plate sensory function
Basal plate- motor function
o initially exists as single layer; pseudostratified
columnar epithelium with very intense proliferative
activity of the cells destined to become neurons. If
they are destined to become neurons, they will
form processes (axons and dendrites).
o Outside the ventricular zone is a layer wherein
there are no cells but just the processes forming the
marginal zone.
o Later, however, this layer would have extensive
mitotic activity so that external to that, another
layer will form called the intermediate layer, which
will lie between the marginal and ventricular layer.
o Both ventricular and intermediate are cellular,
while the marginal only contains processes.

INTERMEDIATE ZONE
o Aka MANTLE layer
o asymmetrical growth
o favors dorsolateral and ventrolateral growth
o SULCUS LIMITANS - demarcation separating the
proliferating cells from the dorsal half to the ventral
half
Dorsal to it will comprise the alar plate
Ventral to it - basal plate.
If a structure is derived from the alar plate or dorsal to sulcus
limitans, it would perform sensory function.
If derived from the ventral half/basal plate = motor function
Proliferation of the cells in the alar and basal plate will reduce
the cavity into a CENTRAL CANAL
o The ventricular zone will become ependymal cells
which line the central canal.
o The alar plate will be the dorsal gray horn sensory
in function.
o Basal plate will become the ventral gray horn
motor in function.
o The marginal zone will become the white matter.



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Each cord segment will be supplying a specific area of the skin
called a dermatome.
As the ventral gray horn is developing, it will form the ventral
root of the spinal nerves which would supply a specific group
of muscles called the myotome of that specific cord segment.
As the cord is forming, the spine is also developing.
1
st
trimester - the root of the first sacral nerve exists below
S1.
2nd trimester and at birth, (B & C), the cord is shorter,
vertebra seems longer, indicating the vertebra is faster in
growth, or the cord slowed down in growth.
There is a discrepancy in the length of the cord and the length
of the vertebra so much so that the cord is almost at the level
of L2 at this time.
o The first sacral nerve will have to travel a longer
way to reach S1.
At birth, it still goes up further up to L1.
In the adult, the tip of the cord is between L1 & L2.
Implications
o Tthe discrepancy in the slower growth of the cord
compared to the vertebra will impose a longer
distance for the spinal nerves from lower thoracic
to the coccygeal segments to exit below the
corresponding vertebra
o Lumbar tap in the child not in the same level as in
the adult. The cord might be hit.
DRG being sensory in fxn coming from the alar plate will be
receiving processes from the pseudounipolar neuron forming
the Dorsal root of the spinal nerve
Ventral Gray Horn sending axons to form the ventral root of
the spinal cord to supply a specific myotome level.
*How will the nerve be able to say where to terminate?
This phenomenon is biochemically dictated. Structures
derived from the neural crest contain in their surface INTEGRINS,
which recognize a specific molecule in the connective tissue at a
specific dermatome level, which in turn contains
LAMININ/FIBRONECTIN containing is a specific amino acid
sequence. This enables the integrins to know where to terminate.
MYELENCEPHALON
Gives rise to the medulla
o Has a portion which is similar to the spinal cord
and a portion where the neural cavity opens to
become the 4
th
ventricle.
o In the portion of the medulla similar to spinal
cord, all structures dorsal to the sulcus limitans
such as the sulcus gracilis and nucleus
cuneatus are alar plate-derived and have
sensory function.
o The gracilis is for conscious propioception on
the legs, while the cuneautus would be
conscious proprioception in the upper
extremities and the trunk.
Upper 1/3 of the medulla, the cavity there opens to form
the 4
th
ventricle.
o Because of the opening of the cavity to
become the ventricle, the alar plate becomes
rotated dorso laterally and becomes lateral to
the sulcus limitans.
o As for the basal plate, it will now become
medial to the sulcus limitans. The orientation
of the alar and basal changes in the upper
medulla.
Lower 2/3 of medulla alar is posterior/dorsal; basal
ventral

SUMMARY of changes in the Myelencephalon (Medulla)

o Nucleus solitarius (CN 7, 9, 10) for taste
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o Descending nucleus of V (trigeminal) for pain
and temperature (face region)
o CN nerves 12, 11, 10, 9 can be found in the
Myelencephalon
METENCEPHALON (Pons and Cerebellum)
Wide cavity
Orientation of alar and basal plate would still be lateral and
medial, respectively
At the region of the pons, CN 5, 6, 7, and 8 can be found
Sensory (CN 5, 8) - alar
Motor (6, 7) basal
RHOMBIC LIP of the ALAR plate proliferative; as it starts to
grow further, it would meet with the rhombic lip of the other
side and cover the posterior surface of the 4
th
ventricle to
give rise to the cerebellum

DEVELOPMENT OF THE CEREBELLUM
outer gray matter, inner white matter
Cells from the intermediate zone would migrate using the
radial glia cells as a scaffold to hold on to while they migrate
external to the marginal zone to form the external/granular
layer.
From this layer of cells, the granule cells, stellate cells and
basket cells will be formed.
From the original intermediate zone, the cells would also
migrate but they migrate outward and would give rise to the
deep cerebellar nuclei and purkinje cells.
It is the POSTEROLATERAL FISSURE and not the PRIMARY
FISSURE that is the 1
st
to form in the cerebellum.
MESENCEPHALON (MIDBRAIN)
The orientation of the alar and basal plate reverts back to the
usual. Alar dorsal; basal - ventral
CN 3 & 4 (Oculomotor and Trochlear) motor; basal plate-
derived
CN 1 & 2 (Olfactory and Optic) cannot be found in the
brainstem because they are sensory cranial nerves whose
ganglion are in the periphery

Inferior colliculus auditory relay nucleus
Superior colliculus visual relay nucleus

DIENCEPHALON
Initially, there exists a demarcation between the
diencephalon and the telencephalon.
However, during development the telencephalic starts to
overhung the diencephalon, and thus the structures of the
diencephalon cannot be seen externally. To see this
structures, one will have to dissect the brain into sagittal or
coronal or longitudinal sections. The diencephalon is covered
by the cerebral cortex.
The diencephalon is largely derived from the alar plate.
Gives rise to the epithalamus, thalamus and hypothalamus
Development of thalamus occurs in an outside-first sequence (most
lateral nuclei develop first, medial nuclei develop last)
Establishment of an orderly map of the sensory world in the thalamic
nuclei (retinotopic mapping, tonotopic mapping)
o Ex. In the lateral geniculate nucleus which receives
signals from the retina, as the images in the retina
are organized, when they are projected to the
lateral geniculate, orderly din.
PROSENCEPHALON
Gives rise to Telencephalon and Diencephalon
Central induction -process of forebrain development
Failure of prosencephalon to undergo cleavage results in
holoprosencephaly (alobar and semilobar)
Develop at 2
nd
month of gestation simultaneous with formation of
facial structures from mesoderm
o Ex. Cyclops; multiple facial clefts; proboscis
Infections may predispose to CNS abnormalities- TORCH
o TORCH (Toxoplasmosis, Rubella, Cytomegalovirus,
Herpes Simplex, Syphilis) to test infectious agents
which the pregnant woman may have had in the
past but can still affect the baby
TELENCEPHALON (CEREBRAL CORTEX)
Outer gray has 6 layers
Inside-out pattern
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Formation of cortical plate at interface of marginal zone and
intermediate zone
Formation of the subplate, a narrow region internal to cortical plate
Marginal zone gives rise to layer 1 of cerebral cortex
Cortical plate gives rise to layers II-VI
Subplate and intermediate zone gives rise to subcortical white matter
1
st
trimester hallmark of a normal brain to have gyri and
sulci/fissures
o Due to limited space in the skull
o When it encounters resistance it would form the
gyri and sulci
o More neurons buried inside the sulci and fissures
o Main fissures seen during the 1
st
trimester
Interhemispheric fissure
Sylvian fissure
Central sulcus
o 8
th
month secondary sulci
o 3
rd
trimester tertiary or all sulci are formed
Center of critical thinking, imagination, analysis, etc
ABNORMALITIES
o Lissencephaly- failure of gyri to form; smooth surfaced
cerebral cortex
o Pachygyria- unusually large gyri
o Microgyria- unusually small gyri
o Schizencephaly- abnormal patterns of sulcal and gyral
development with unilateral or bilateral clefts in cerebral
hemisphere
Parameters in brain organization:
Density or Number of neurons
o Neurons terminally differentiated and thus will
not undergo mitosis once formed
o 6 months of gestation overproduction of neurons;
afterwhich, there will be selective apoptosis of
neurons that are not good/useful
Pattern of axon and dendrite branching
o Age 2-3 y.o complete neurons with dendritic and
axonal branching
Pattern of synaptic contacts
o occurs throughout life
o Neurons are always open to new learning
experiences; synaptic contacts can be
fashioned/remodeled
Lumosity website (plasticity of the
brain!) haha. May free app na ganito

Factors affecting synaptic stabilization
Critical period refers to time period when these types of
plastic changes occur; varies from region to region
o Ex. Baby with congenital cataract or severe myopia
of left eye
o as the baby grows the impulses from the right eye
would have to establish synaptic stabilization in the
visual centers in the cortex. But since the left eye is
severely myopic, whatever stimulation it receives is
not enough to send synaptic contact to the cerebral
cortex. If this is not treated early, the entire visual
cortex will be taken over by the good eye so much
so that if later corrective lenses were given, wala
nang pupuntahan na visual cortex kasi kinuha na ng
right eye yung buong area. (This clinical condition is
called AMBLYOPIA)

PLASTICITY
o alterations in selective neuronal death, axonal
simplification and retention of transient axonal
branches and synapses that would otherwise be
lost
o When someone tells you PLASTIC NA PLASTIC KA,
tanungin mo, alin, yung brain ko? and if he/she
says Yes, reply with a Thank you very much for it
is a compliment. Pag sinabi niyang hindi ang brain
mo, SAMPALIN MO NA. kasi iniinsulto ka. (Dra
Lumitao, 2013)

Synaptic development parallels cellular proliferation and migration;
maximal during six months after birth; vulnerable to perinatal
hypoxia, malnutrition and environmental toxins

Myelination from six month of life, peaks from birth to first year;
continues into adulthood; motor and sensory tracts mature early;
affected by leokodystrophies, phenylketonuria and malnutrition
o Myelin is made of lipid. So defect in metabolism of
lipid can affect myelination of nerve tracts.
VENTRICULAR SYSTEM
Normally, should be patent so the CSF can circulate
Any abnormality in the Ventricular system is called
HYDROCEPHALUS
o Treated by shunting of the flow of the CSF.
Otherwise, the trapped CSF will cause pressure in
the developing neurons and then atrophy
o OBSTRUCTIVE NON COMMUNICATING
HYDROCEPHALUS
When there is atresia of the cerebral
aqueduct, the CSF cannot circulate, there
will be dilation proximal to the
obstruction
Congenital aqueductal stenosis
o NON-OBSTRUCTIVE COMMUNICATING
HYDROCEPHALUS
No obstruction but there is abnormality in
the transfer of the CSF from the Sub
arachnoid to the venous system