Histology of

Central Nervous
System (CNS)

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 BRAIN OVERVIEW
– Trillion interneurons fill the brain
– Brain Parts:
– Cerebrum
– Diencephalon
– Cerebellum
– Midbrain
– Pons
– Medulla oblongata
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 BRAIN
– externally, the cerebral hemispheres reveal several
elevations and depressions known as Gyri and
Sulci, respectively.
– The brain stem is the solid-looking structure along the
base of the brain, and continuous with the spinal cord at
lower end. Has three regions; each about one inch long.

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4
 CEREBRAL HEMISPHERES
– Consists of a convoluted cortex of grey matter overlying the
central medullary mass of white matter.
– The white matter conveys fibers between different parts of the
cortex
and to and from other parts of the CNS.
– Histologically, the neurons of the cerebral cortex are divided into five
different morphological types which are arranged in several layers.
– In mammals, there has evolved the so-called neocortex consisting of
six layers of neurons.
– Includes the sensory and motor areas of the neocortex as well as
association cortex and in humans, which constitute about 90% of
the cerebral cortex.
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 Section of cerebral neocortex, showing cuts of
two gyri. The pale cortex follows along the
contours of the gyri. White matter (composed of
nerve processes) lies below and stains a darker pink.

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 NEURON TYPES IN CEREBRAL CORTEX
– The cerebral cortex consists of five main types of neurons;
the stellate cells and pyramidal cells being by far the most
common types.
1. STELLATE/GRANULE CELLS
– are small granular neurons (about 8 µm in diameter) with
a short vertical axon & several short branching dendrites
giving the cell body a characteristic star-shaped.
– receive information & synapse locally, and hence are types
of interneurons.
– highly populated in sensory regions and bring complexity
and granularity to the sensory cortex.
. 86
Stellate/granule cells

9
 2. PYRAMIDAL CELLS
– have pyramid-shaped cell bodies whose apex is
being directed toward the cortical surface.
– From the apex, a thick branching dendrite pass towards
the surface where it has an array of fine dendritic
branches.
– In addition, short dendrites arise from the edges of the
base and ramify laterally.

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PYRAMIDAL CELLS

11
– The size of pyramidal cells varies from small to large the
smallest tend to lie more superficially and their size
progressively increase as we go from superficial to deep.
– the smallest pyramidal cells are about 10 to 15 µm
in diameter.
– The upper motor neurons of the motor cortex known
as Betz cells are the largest, giant pyramidal cells,
whose long axon projects inward to synapse in spinal
cord.

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Pyramidal Cells of Betz in the Cerebral Cortex

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Cerebral cortex: (a): Important neurons of the cerebrum are pyramidal neurons (P), which are arranged
vertically and interspersed with numerous glial cells in the eosinophilic neuropil. X200. H&E. (b): From the
apical ends of pyramidal neuron, long dendrites extend in the direction of the cortical surface, which can
be best seen in thick silver-stained sections in which only a few other protoplasmic glial cells are see9n6 .
X200. Silver.
 3. FUSIFORM CELLS
– Are spindle-shaped cells oriented perpendicular to the
surface of the cortex.
– the axon arises from the side of the cell body and passes
superficially to synapse with dendrites of horizontal
cells
4. CELLS OF MARTINOTTI
– are polygonal cells found through out the cortex
– with a few short dendrites and the axon extends outward
to the cortical surface and bifurcate to run horizontally,
usually in the most superficial layer.

98
Fusiform cells

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Cells of Martinotti

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 5. HORIZONTAL CELLS OF CAJAL
– are small spindle-shaped cells oriented parallel to
the cortical surface.
– are the least numerous cells found in the superficial
layer where their axon pass laterally to synapse with
the dendrites of the pyramidal cells.

NEUROGLIAL CELLS OF CEREBRAL CORTEX

– In addition to neurons, the cortex contains supporting
neuroglial cells, i.e. astrocytes, oligodendroglia and
microglia.

102
 The six histological layers of Neocortex
– differ in neuron morphology, size and population density.
– merge with one another rather than being highly
demarcated
– vary somewhat from one region of the cortex to another
depending on cortical thickness and function.
1. THE MOLECULAR or PLEXIFORM LAYER: (10-
15%)
– is the outermost /superficial layer of the cortex
– the subpial layer or zone
– formed of primarily nerve fibers and neuroglial
elements.
– it is a synaptic field, consisting several sections of nerve
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2. THE EXTERNAL (OUTER) GRANULAR LAYER (10-20%)
– it is formed of mainly small stellate neurons, small
pyramidal cells or triangular cells whose dendrites
terminate on the molecular layer.
– and cells of Martinotti and nerve fibers.
– it is well developed in sensory cortex

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 3. THE EXTERNAL/OUTER PYRAMIDAL CELL LAYER (30%)
– it is formed of typically well-formed pyramidal
neurons and cells of Martinotti.
– the base of the cells are directed internally

– composed of two sublayers in motor cortex:

– Superficial layer of medium sized pyramidal cells:

– Deep layer of larger pyramidal cells

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 4. THE INNER/INTERNAL GRANULAR LAYER: (10%)
– chiefly composed of densely packed stellate cells and glial
cells
– dendrites of these cells receive axon terminals of
thalamo-cortical axons (thalamo-cortical ramifications)

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 5. THE INNER PYRAMIDAL CELL LAYER
(INTERNAL PYRAMIDAL OR GANGLIONIC LAYER:
(20%)
– it is formed of large pyramidal cells called Betz cells about
85 micrometers with their apex directed outward and
their bases inward.
– consists Giant Pyramidal cells of Betz (origin of
the pyramidal tract in motor cortex)
– interspersed are stellate/granule cells and
cells of Martinotti,

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6. THE POLYMORPHIC/MULTIFORM CELL LAYER: (20%)
– named for the wide variety of cells with differing
morphological forms (neurons of variable shape and
sizes) found in the layer.
– Also called layer of polymorphic cells
– contains numerous small pyramidal cells and cells of
Martinotti, as well as stellate cells especially
superficially, and fusiform cells in the deeper part.

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26
 CEREBRAL CORTEX
1

7
27
The six histological layers of Cerebral Cortex

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Cerebellum

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 CEREBELLUM
– Cerebellum is composed of four neuronal layers:
(three in the cortex (grey matter) and one layer in
the medulla (white mater) made up of five main
types of neurons:
1. Granule cells
2. Stellate cells
3. Purkinje cells
4. Basket cells and
5. Golgi type 2 cells (cells of Gehucten)
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 CEREBELLAR GREY MATTER:
– composed of three neuronal layers and small nuclei of glial cells.
1. Molecular layer: few cells and few myelinated fibers
– composed of stellate (in the superficial cell layer ) & basket cells (in
the deep aspect)
2. Purkinje or Middle Ganglionic Layers
– consists of single row of large, flask shaped bodies with 2 processes
3. Granular Layer
– closely packed heterochromatic nuclei resembling lymphocytes,
irregular light spaces that constitute the “islands” or “glomeruli”
– Granule Cells: small, multipolar cells with 3 or 4 dendrites and
unmyelinated axons
Golgi Type II cells or cells of Gehucten: cells with vesicular nuclei and
chromophilic cell bodies.
– Mossy fibers: thick fibers and synapse with the granule cells
– Climbing Fibers: wind around & terminate on Purkinje cell
Purkinje cell with a rounded cell body, a slender axon and three to five
main dendrites that divide into an elaborate dendritic arborizations.

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Folia of Cerebellum: a core of white matter covered by a
grey matter consisting of three neuronal layers

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Diagram Showing Histological Layers of Cerebellum

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The Three Neuronal Layers Of Cerebellar Cortex:

Outer molecular layer

Purkinje cell
layer

Inner granular
layer 35
MICROSCOPIC STRUCTURE OF THE CEREBELLAR CORTEX

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MICROSCOPIC STRUCTURE OF THE CEREBELLAR CORTEX
(OUTER GREY MATTER OF CEREBELLUM)
1- THE OUTER MOLECULAR LAYER:
– IT IS FORMED OF THE FOLLOWING:
– the molecular stellate cells (in
the superficial cell layer )
– the basket cells (in the deep
aspect)
– the neuroglial cells
– the dendrites of the purkinje
cells
– the axons of the granule cells
– the terminal ends of the climbing 142
2- THE MIDDLE PURKINJE CELL LAYER:
– the purkinje cell is pyriform in shape, its axon terminates
around the cerebellar nuclei.
– the cell bodies are arranged in a single layer widely spaced
away from each other.
– the dendrites of purkinje cells form the main bulk of
thickness of the molecular layer.
3- THE INNER GRANULAR LAYER:
– it is formed of very small nerve cells, granule cells about 5-
7μm in diameter
– they are packed together and their bodies receive fibers
from the different cerebellar peduncles, which are
called the mossy fibers.
– the axons of such cells are in synaptic connections with
dendrites
the of the purkinje cells. 143
BRAIN VENTRICLES AND CHOROID PLEXUSES

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 CHOROID PLEXUSES
– a highly specialized tissue that projects as elaborate folds
with many villi into the four large ventricles of the brain.
– found in the roofs of the third and fourth ventricles and in
parts of the walls of the two lateral ventricles, all regions
in which the ependymal lining directly contacts the pia
mater.
– Each villus of the choroid plexus contains a thin layer of
well-vascularized pia mater covered by cuboidal
ependymal cells.
– The main function of the choroid plexus is to remove
water from blood and release it as cerebrospinal fluid
(CSF).
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 CHOROID PLEXUS
– constitutes pseudoglandular epithelia specialized for
secretion of CSF.
– found in the roof of brain ventricles where the pia mater
and ependymal cells come close together with out
intervening nervous tissue.
– This fused meningeal and ependymal tissue is called
tela choroidae.
– secrete the cerebrospinal fluid (CSF)
– consists of loose areolar CT core rich in fenestrated blood
capillaries covered by a simple cuboidal epithelium
formed by the modified ependymal cells known as
Tanicytes or choroid ependymal cells.
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Section of choroid plexus containing pial cells surrounding fenestrated
capillaries supported in loose areolar tissue externally covered by157
 MEDULLA OBLONGATA
– is the most distal part of the brain stem continues with the
spinal cord at its lower end in the foramen magnum.
– roughly divided in to upper open part and lower closed
part.
– All the ascending (sensory) and descending (motor)
pathways in the spinal cord pass through the medulla.

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 The Lower medulla:
– Its grey matter is still central roughly resembling the
characteristic butterfly shape seen in the sections of spinal
cord.
– The ventral grey matter horns contain cell bodies of
lower motor neurons running in the spinal accessory and
first cervical nerves.
– The medulla also contains various tracts and nuclei of the
eighth to twelfth cranial nerves.

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Medulla Spinalis

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 PONS
– In TS section, it comprises two parts: a bulky ventral
region (the basal pons) and a smaller dorsal
(tegmental) region.
The Basal Pons
– consists of criss-crossing bundles of longitudinal and
transverse fibers between which lie collections of
neuron cell bodies known as pontine nuclei.
– The longitudinal fibers consist of descending
fibers of two main types:
1. Axons from the motor cortex passing down through the
internal capsule break up into small bundles here in the pons.
These fibers on leaving the pons, converge to form the
characteristic pyramids (pyramidal tracts) of the medulla and
then synapse54 with lower motor neurons of the ventral horns of
the spinal cord.
2. The second group of longitudinal fibers include descending
fibers originating in various areas of the cortex and
synapse in the pontine nuclei from which fibers then pass in
the transverse bundles, crossing the midline to enter the
cerebellum via the middle cerebellar peduncles.

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 MIDBRAIN
– is the most cranial portion of the brain stem, lying between
the diencephalon proximally and the pons distally.
– On each side, the midbrain contains a red nucleus and a
substantia nigra.
1. Red nucleus contains numerous blood vessels and
receives info from the cerebrum and cerebellum and
issues of subconscious motor commands concerned with
muscle tone & posture.
2. Lateral to the red nucleus is the melanin-containing substantia
nigra which secretes dopamine to inhibit the excitatory neurons of
the basal nuclei.
– Damage to the substantia nigra would cause what?
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TS of Midbrain
 Substantia nigra
– is a large mass of grey matter extending through out the
midbrain lateral to the red nucleus.
– a nucleus on each side of the midbrain
– On each side, it divides between the cerebral peduncle
ventrally and the red nucleus dorsally.
– In sections of midbrain, it is recognized by the dark
brown/black pigment, the melanin from which its name
derives.
– Has extensive connections with the cortex, spinal cord,
corpus striatum, basal nuclei and reticular formation.
– Appears to play an important part in the fine control of
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motor function.
 Neurons of Substantia nigra
– are multipolar in form and in adults their cytoplasm
contains numerous granules of melanin pigment.
– The pigmented neurons contain and secretes dopamine
which act as a neurotransmitter causing inhibitory effects
on the excitatory neurons of the basal nuclei particularly
corpus striatum.
– DOPA (dihydroxyphenylalanine) is a precursor of dopamine and also
melanin.
– The melanin of substantia nigra neurons may merely
represent a residual product of normal metabolic activity;
this is supported by the fact that very little melanin is
present at birth with the amount increasing considerably
during the childhood and thereafter rising at a lower rate
into old age.
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 Parkinson’s Disease
– a debilitating disorder characterized by tremor, muscular rigidity and
impaired speed and precision of motor functions.
– associated with degeneration of neurons in substantia nigra and
marked reduction in dopamine synthesis.
– symptoms can be alleviated by the drug L-dopa , a dopamine
precursor which crosses the blood brain barrier.
Damage to substantia Appearance of symptoms of
nigra Parkinson’s disease: shiver,
slow movement, inability to
move, rigid walk, reduced facial
expression
Decrease in
dopamine secretion

Increased activity of Gradual increase

basal nuclei in muscle tone 61
 DIENCEPHALON
HISTOLOGY OF THALAMUS, HYPOTHALAMUS
& EPITHALAMUS

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 THALAMUS (THAL-a-mus, inner chamber),
– The two thalami are large masses of grey matter lying on
each side of the third ventricle.
– Comprise the main bulk (about 80% )of the diencephalon,
the central core of the cerebrum.
– Each measures about 3 cm (1.2 in.) in length and consists
of oval mass of gray matter organized into nuclei with
interspersed tracts of white matter.
– A bridge of gray matter called the intermediate mass
(interthalamic adhesion) joins the right and left halves of
the thalamus in about 70% of human brains.
– Constitutes an extremely complex relay and integration
center for information from almost all parts of the CNS.
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Thalamus

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 Thalamus – It is a
relay station to the
cerebrum for all
varieties of sensory
input, except
olfaction.

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 THALAMUS
– A longitudinal Y-shaped sheet of white matter called
the internal medullary lamina divides the gray matter of
each half of the thalamus into medial and lateral halves.
– It consists of myelinated axons that enter and leave the
various thalamic nuclei.
– Axons that connect the thalamus and cerebral cortex pass
through the internal capsule, a thick band of white matter
lateral to the thalamus.
– Functionally subdivided into a large number of
nuclei including reticular, and motor nuclei as well as
specific sensory nuclei.
– Typical thalamic nucleus consists of a dense aggregation
of neuron cell bodies criss-crossed by tracts of
afferent
and efferent nerve fibers. 68
Nuclei of Thalamus

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 Nuclei of Thalamus
1. Specific sensory relay nuclei
– Ventral posterior nucleus – projects to somatosensory area
– Lateral geniculate nucleus – projects to visual cortex
– Medial geniculate nucleus – projects to auditory cortex
2. Associated nuclei – receives inputs from cortical areas
– Ventral lateral nucleus
– Pulvinar nucleus
3. Nonspecific projection nuclei – fibers project to
association cortex & limbic system
– Anterior nuclei
– Medial nuclei
– Intralaminar & reticular nuclei
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2. HYPOTHALAMUS

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HYPOTHALAMUS

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Neurosecretory Cells of Hypothalamus

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 3. EPITHALAMUS
– Lies above the thalamus
– The dorsal portion of the diencephalon
that includes a thin roof over the third
ventricle.
– The pineal gland outpouches from the
posterior end of the epithalamus.
– pineal gland releases melatonin (involved in sleep/wake
cycle and mood).
– The inside lining of the roof consists of a
vascular choroids plexus where CSF is produced.
– Epithalamus contains a structure called the
EPITHALAMUS

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 SPINAL CORD
– Transverse section through the spinal cord reveals:
1. The central mass of grey matter
– surrounds the central canal of spinal cord which is lined by
ependymal cells
– has the shape of a butterfly or H-shape with two or three
horns on each side
– made by a pillar of cell bodies of afferent & efferent
neurons and neuroglia.
– surrounded by the fibers of neurons which form white
matter
– on each side contains: anterior and posterior horns at all
regions and lateral horn at some (thoracic, upper
lumbar
and sacral) regions. 27
Transverse section through the spinal cord

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 There are three main horns of the grey matter:
1. The Anterior Horn, or The Ventral Horn
– never reach the surface of the spinal cord (motor)
– most prominent and contains the cell bodies of the large lower
somatomotor neurons.
2. The Posterior Horn, or The Dorsal Horn:
– reaches the surface of the spinal cord (sensory)
– much less prominent and contain the cell bodies of small
second order sensory neurons, which relay sensory information
to the brain from primary afferent neurons for the modalities of
pain and temperature and crude touch, whose cell bodies lie in
the dorsal root ganglia.
3. The Lateral Horn
– mainly found at the thoracic & upper lumbar regions
– contains the cell bodies of preganglionic, sympathetic efferent
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neurons (sympathetic outflow from the cord)
– The volume of grey matter is much more extensive in the
cervical and lumbar regions:
– reflected in much greater diameter of the spinal cord in these
areas
– corresponding to the sensory and motor innervation of the
limbs
– THE PERIPHERAL WHITE MATTER:
– consists of ascending tracts of sensory fibers and descending
motor tracts
– its volume increases progressively from the sacral to cervical
regions, because passing up the spinal cord toward the brain
more and more fibers enter the cord.
– it is arranged in three main white columns

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1- The Dorsal/Posterior White Column:
– is completely separated from the lateral column by the dorsal horn
– convey sensory fibers of proprioception, vibration and
discriminatory/fine touch to the medulla, where they synapse with
second order neurons in the gracile and cuneate nuclei.
– in the cervical region divided into the medial fasciculus gracilis
conveying fibers from the lower limbs, and the lateral fasciculus
cuneatus, conveying fibers from the upper limbs.
2- The Lateral Column:
– made up of various ascending tracts, notably the lateral
spinothalamic tract for pain and temperature and ventral
spinothalamic tract (light/crude touch) and spinocerebellar tracts
(for proprioception).
3- The Anterior Column or the Ventral Column: contains corticospinal
tract (motor)- is in free communication with the lateral column and
called the ventro-lateral column.
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COMPARISON BETWEEN THE DIFFERENT LEVELS OF THE SPINAL CORD

FEATURES CERVICAL THORACIC LUMBAR SACRAL

1 EXTERNAL large small and large Small and oval,
SHAPE AND SIZE and round and surrounded
oval round by nerve
fibers
2 DORSAL HORN thin and thin and thick and Small and
divergent parallel parallel
divergent
3 LATERAL HORN absent present Present in absent
upper
part
4 VENTRAL HORN thick thin and thick and Small and
parallel parallel
divergent
5 RELATION white grey and grey matter grey matter is
BETWEEN matter is white matters is more than more than
GREY AND more than are more or white matter white matter
WHITE grey less equal
MATTER matter
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6 POSITION OF THE posterior anterior central central
 SPINAL CORD AT
DIFFERENT LEVELS
(MYELIN STAIN)

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GOOD
STUDY

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