INTRO TO NEUROLOGY (Snell’s Neurology)

 Both brain & spinal cord are covered by meninges and suspended in CSF
Autonomic Nervous System
innervates the body's involuntary structures, such as the heart, smooth muscle, and
glands.
It is distributed throughout the CNS and PNS
CNS - brain & spinal cord
CNS interior is organized into gray and white matter:
Gray matter- consists of nerve cells embedded in neuroglia.
White matter -consists of nerve fibers embedded in neuroglia and is
white in color because of the presence of lipid material in nerve fiber
myelin sheaths.
PNS - cranial & spinal nerves & their ganglia

ls divided into two parts, sympathetic and the parasympathetic

Spinal Cord
- situated within the vertebral canal of the vertebral column
- is surrounded by 3 meninges: dura mater; arachnoid mater, pia mater.
- It begins superiorly at the foramen magnum in the skull, where it is
continuous with the medulla oblongata of the brain.
- It terminates inferiorly in the lumbar region. Tapers into conus medullaris,
from the apex of which filum terminale (prolongation of the pia mater),
descends and attach to the back of coccyx
- 31 pairs of spinal nerves
= attached by the anterior (motor roots) & posterior (sensory roots)
- possesses posterior root ganglion, give rise to PNS and CNS fibers

Spinal Cord Structure

Gray matter - inner core; H-shaped pillar with anterior and posterior gray horns.
Gray commisure - unites this gray horns. Containing small central canal
White matter - outer core; divided into anterior, lateral and posterior white columns

Brain
-lies in the cranial cavity, continous with spinal cord through the foramen magnum
- is surrounded by 3 meninges: dura mater; arachnoid mater, pia mater.
- 3 major division: Hindbrain, midbrain, forebrain
- 3 brainstem (Medulla oblongata, pons, midbrain)

Hindbrain
Medulla Oblongata
- conical in shape. Connects the pons superiorly to the spinal cord inferiorly
- conttains collections of neurons, “nuclei”and serves as a conduit for ascending and descending nerve fibers.

Pons
- situated on anterior surface of the cerebellum, inferior to midbrain, superior to medula oblongata
- with large number of transverse fibers on its anterior aspect connecting two cerebellar hemisphere
- contains many nuclei and ascending and descending nerve fibers

Cerebellum
- lies within posterior cranial fossa of the skill, posterior to the pons & medulla oblongata.
- consists of 2 laterally placed hemisphere, connected by VERMIS.
- connected to the midbrain by Superior cerebellar peduncles
- connected to the pons by middle cerebellar peduncles
- connected to the medulla by inferior cerebellar peduncles
- PEDUNCLES - composed of large bundles of nerve fibers connecting cerebellym to the remaining CNS
- CORTEX - surface layer of each cerebellar hemisphere
-composed of gray matter.
-thrown into folds, separated by transverse fissures.
- some is embedded in white matter; largest of these is known as DENTATE NUCLEUS
FOURTH VENTRICLE - cavity filled with CSF, sorrounding medulla oblongata, pons, cerebellum
Connected superiorly to the third ventricle by CEREBRAL ADQUEDUCT
Inferiorly with central canal of spinal cord
Communicates with subarachnoid space through 3 openings in the inferior part of roof
Midbrain
- narrow part of the brain that connects the forebrain to the hindbrain
- contains many nuclei and bundles of ascending and descending nerve fibers.
Cerebral aqueduct -connects third and fourth ventricles.

Forebrain
Diencephalon
- central part of forebrain
- almost completely hidden from the surface of the brain
- Composed of DORSAL THALAMUS & VENTRAL HYPOTHALAMUS
Thalamus - large, egg-shaped mass of gray matter that lies on either side of third ventricle.
- anterior end of thalamus forms the posterior boundary of interventricular foramen [-opening between third and lateral ventricles]

Cerebrum
- largest part of the brain
- consists of two cerebral hemispheres, connected by mass of white matter, Corpus callosum
- each hemisphere extends from from to occipital bone in the skull, superior to anterior and middle cranial fossal posteriorly lies above
tenorium cerbelli
- separated by deep cleft, longitudinal fissure, into which falx cerebri projects
- surafe is cortex, which is composed of gray matter
- Cortex is thrown into folds (gyri), separated by fissures or sulci. This increases surface area of the cortex
- Basal nuclei or ganglia - large masses of gray matter, found within central core of white matter
- Corona radiata - fan shaped collection of nerve fibers, passes in the white matter to form cerebral cortex
- converges on basal nuclei and passes between them as internal capsule

-each cerebral hemisphere has cavity called LATERAL VENTRICLE

- communicates with the third ventricle though INTERVENTRICULAR FORAMINA

Brain Structure
Inner core - white matter; Outer core - gray matter
Important gray matter (situated deeply within white matter): gray cerebellar nuclei in the cerebellum
gray thalamic, Caudate
Lentiform nuclei in the cerebrum

MAJOR DIVISIONS OF THE PERIPHERAL NERVOUS SYSTEM

Cranial and Spinal Nerves
 Each spinal nerve is connected to the spinal cord by 2 roots: ANTERIOR ROOT & POSTERIOR ROOT
 Anterior root - bundles of nerve fibers carrying nerve impulse away from the CNS- [efferent fibers]
- carry impulse to skeletal muscles and causes them to contract [motor fibers]
 Posterior root- budles of nerve fibers carrying nerve impulse toward CNS -[afferent fibers]
- carry impulse about sensation of touch, pain, temperature, and vibration-[sensory fibers]
 Cell bodies of these nerve fibers are situated in swelling on posterior root called POSTERIOR ROOT GANGLION
 Spinal nerve root pass from spinal cord to their respective intervertebral foramina, where they unite to form a spinal nerve [has both
sensory and motor fibers]
 There is disproportionate growth in vertebral column during development. The length of the root increases progressively downward.
In the upper cervical region, SPINAL NERVE ROOTS are short and horizontal
In the LUMBAR & SACRAL NERVE ROOTS, below level of termination of cord, form a vertical leash of nerves aroung FILUM
TERMINALE = theses lower nerve roots are called CAUDA EQUINA

Cranial nerve - exits through foramina

Spinal nerve - exits through intervertebral foramina → → spinal nerve: Anterior Ramus & Posterior ramus [both has motor & sensory fibers]
Posterior ramus - supply muscles and skin of the back
Anterior ramus- supply musckes anteriorly and skin overlying anterolateal body wall and all muscles & skin of limbs
- joins one another at the root of the limbs to form NERVE PLEXUS
Cervical & brachial plexus = found at the root of upper limbs
Lumbar & sacral plexus = found at the root of lower limbs

Ganglia
 Sensory ganglia of spinal nerve [posterior root ganglia]
- are fusiform swellings on posterior root of spinal nerve.
- found along the course of cranial nerves V, VII, VIII, IX, and X

 Cranial nerves & autonomic ganglia

- irregular in shape, situated along the course of efferent nerve fibers of ANS
- found in paravertebral sympathethic chains around the roots of great visceral arteries in the abdomen, embedded within walls of
viscera

EARLY DEVELOPMENT OF THE NERVOUS SYSTEM

Entoderm (innermost layer) → GI tract, lungs, liver Fusion start at midpoint, extends cranialy & caudally.
WHY?
Mesoderm → muscles, connective tissuse, vascular system
So that cavity can remain in communication with amniotic
cavity through ANTERIOR & POSTERIOR NEUROPORES [closses
@ 4th week]
Ectoderm (outermost) → nervous system
NT closses @
3rd week: ectoderm on dorsal surface of embryo tickens to form NEURAL PLATE
28 days
[pear shaped, wider cranially. Develops longitudinal neural groove→ neural folds→ neural folds fusing →NEURAL TUBE]
# Neural plate “invagination” → Neural groove + some cells forming lateral margin of plate,
DO NOT INCORPORATE in neural tube, instead form a strip of ectodermal cells lying bet. neural tube → Neural crest
→ Posterior root ganglia, autonomic gnaglia, cells of suprarenal medulla, melanocytes

Neural tube “proliferates” → dilation and formation of 3 primary brain vesicles: forebrain, midbrain, hindbrain
Spinal cord and Caudal portion of brainstem - develops in a straightforward organization,
mantle layer → basal plate (future anterior horn) & alar plate (future posterior horn)

+ @ 10th week Interhemispheric

fissure
Transverse
fissure

Endbrain From the walls of endbrain

From residuals of central lumen of endbrain

Interbrain

Separated by SULCUS LIMITANS

 Bending and folding mechanism predominates throughout both developments to yeild an overall CNS enlargement without
proportional increase in its volume
 The bending provess of developing hemisphere takes place around its center which cooresponds to the each Thalamus
 Folding process acting on its surface give rise to the sulci, which delimit the cerebral convulutions, or gyri, significantly
enlarging its cortical area.
 [fissures→ sulci formed according to sequence]
 4th- 5th months of fetal life, the first definite sulci (olfactory, calcarine, parieto-occipital, cingulate, and central)
begin to appear initially as points or grooves, followed by further secondary and tertiary furrows, some developed
only after birth
 development of the sulcal pattern in the medial surfaces seems to be particularly influenced by the development of the
corpus callosum
 burying process is believed to result from a trade-off between the various folding pressures that occur during brain growth =
presence of some “buried” gyri

MANTLE LAYER of Neural tube - forms gray matter

MARGINAL LAYER - forms the white matter
The Cerebral Hemispheres
- most develpmed part of human nervous system
- corresponds to a large mass of neuronal tissue with a C-shaped format which medially wraps the ipslateral thalamus with lateral
ventricle in between.
- has cerebral cortical mantle as its surface
- characterized anteriorly by the frontal and temporal poles; posteriorly by occipital lobe
- it harbors the basal ganglia (caudate nucleus, putamen, nucleus accumbens, globus pallidus amygdala, and claustrum)
- both hemisphere connencted by Corpus callosum along the midline
- each hemisphere has superolateral surface, medial surface, and inferior/basal surface

The Meninges, the Subarachnoid Space, and the Main Cerebral Fissures
CNS is surrounded externally by the three meninges: the pia mater, the arachnoid, and the dura mater
Pia mater - firmly attached to the surface of the CNS along its whole extent, depressions, and recesses, and is responsible for the
consistency and relative endurance of the CNS surface.
Arachnoid - completely covers the CNS as a tight envelope, harboring the subarachnoid space and with the cerebrospinal fluid (CSF)
Dura mater - most superficial of the meninges, being the thickest and the only one that contains blood vessels and nerves.
- the dura that covers the brain is formed by 2 leaflets; spinal cord dura is composed of only one leaflet.
Falx - separates the two cerebral hemisphere
Tentorium - supports both temporo-occipital surfaces.

Three major cerebral fissures:

1. lateral or Sylvian fissure - along the superolateral surface
2. interhemispheric or longitudinal fissure - along the medial surface
3. transverse fissure of Bichat - within cerebral basal surface

-these fissures constitute well-defined and anatomically constant natural spaces, and they harbor the main supratentorial
subarachnoid cisterns

Harbors the most

Lateral (sylvian) fissure - classically divided into an anterior part (sphenoidal part and as stem of sylvian fissure) --
Lateral/ posterior part basal part of sylvian
Runs obliquely along superolateral
Harbors the largest part of sylvian cistern, with the brain surface separating the surfaces cistern with the initial
superior & inferior branches of middle cerebral artery of the frontal and temporal lobes, segment of MIDDLE
at its base (M2 segment), with its frontoparietal and Underneath sylvian vein CEREBRAL ARTERY
temporal branches (M3) segment looping around (M1 segment)

External to lateral sylvian fissure - has the most distal branch of middle cerebral artery (M4)
segment

Interhemispheric or longitudinal fissure

Corpus callosum - separates the medial surface of both cerebral hemisphere
Falx cerebri - divides hemisphere longitudinally. Does NOT reach the superior surface of corpus callosum, hence CINGULATE
GYRI is attached along the midline
- Contains callosal and Interhemispheric cisterns
- harbors pericallosal and callosmarginal arteries and the distal branches of both anterior cerebral arterues (A2, A3,
A4, A5 segment of cerebral arteries)
Transverse fissure of Bichat
- located around inner basal aspects of both cerebral hemispheres, resembling 2 horseshoes with anterior concavities and with
common median part.
 Neurons and Neuroglia
- nerve cells; excitable cells that are specialized for reception of stimulo and conduction of nerve impulse.
- Each posses a CELL BODY from which one or more processses called NEURITES projects.
- Neurites responsible for receiving information and conducting it toward the cell body are DENDRITES
- fine terminal branches found at the preripheral end of the axon
- Single long tubular neurites that conduct impulsees away from the cell body is AXON
- Axon and Dendrites are commonly referred as NERVE FIBERS
- 5nm - 135nm in diameter; Neurites may extend over 1m

into two branches

Elongated cell body

1m lengh in extreme

Pyramidal cell of
Cerebral cortex;
Often inhibitory in function
Purkinje cells

Neuronal Structure
Nerve Cell Body
Volume of cytoplasm within the nerve cell body is often far less than the total volume of cytoplasm in the neurites.

Cell bodies: 5nm - 135 nm in diameter

A discrete group of nerve

cell bodies in CNS
In mature Neurons, the chromosomes no longer duplicate themselves and function only in gene expression
CHROMOSOMES are not arranged as compact structures but exist in an uncoiled state.
NUCLEOLUS synthesiszes rRNA and assistes with ribosome subunit assembly
-large size of nucleolus probably is due to high rate of protein synthesis, which is necessary to maintain protein level
Nuclear envelope - is continous with the cytoplasmic rough or rough RER. The enelope is double layered and possesses fine
nuclear pores [materials can diffuse into and out of nucleus]

Cytoplasm - Inlusions:
1. Nissl substance
Axon hillock -- region close to the axon
2. Golgi complex
3. Mitochondria
4. Microfilaments
5. Microtubules
- Microtubules and microfilaments - provide a stationary track that permits specific organelles to move by molecular motor.
-Cell transport involves: movement of membrane organelles, secretory material, synaptic precursor membrane, large dense
core vesicles, mitochondria, and SER.

-Rapid tramport (100 to 400 mm/day) is mediated by two motor proteins associated with the microtubule (ATP)-ase sites
Anterograde movement(away from cell) - Kinesin-coated organelles are thought to move toward one end of tubule
Retrograde movement( toward the cell) - dynein-coated organell move toward other end of tubule.
- direction and speed of the movement of an organelle can be brought about by the activation of one of the motor proteins
-Slow transport (0.1 to 3.0 mm/day)- Involves the bulk movement of the cytoplasm and includes the movement of
mitochondria and other organelles.
- occurs only in the anterograde direction.
- The molecular motor has not been identified but is probably one of the kinesin families.

6. Lysosome
3 forms of lysosome:
Primary: which have just been formed
Secondary: contains partially digested material (Myelin figures)
Residual bodies: enzymes are inactive and bodies have evolved from digestible materials such as pigments and bile
7. Centrioles
8. Lipofucin, melanin, glycogen, and lipid

Plasma Membrane
Plasma membrane - forms continous external boundary of the cell body and its processes.
- site for initiation and conduction of nerve impulse.
- membrane is about 8nm thick, which is too thin with light microscope appears as two dark lines with a light line between them

Plasma membrane is composed of inner & outer layer of very loosely arranged protein molecules, each layer being 2.5nm thick,
separated by middle layer of lipid about 3nm thick.

Lipid layer - made of 2 rows of phospholipid molecule arranged so that their hydrophobic ends are in contact with protein layer.
Carbohydrate molecules are attached to the outside of
plasma membrane and linked to the proteins or lipids
forming known as CELL COAT or GLYCOCALYX
Resting state (unstimulated state)
K+ diffuse through plasma membrane from cytoplasm to
tissue fluid
K +is much greater than N+ ions → passive efflux of K+
is greater than influx of Na+

Steady potential difference of 280mV

Inside the membrane is negative
K+ channel gates open wider than Na+ channel gates,
which nearly closed → K+ diffuse more readily tnan Na+

Resting membrane potential

Nerve fiber is polarized, potential difference across plasma
membrane (axolemma) is -80mV, with the outside of
membrane positive to the inside

Excited (stimulated)
- rapid change in membrane permeability to
Na+
Na+ diffuse through plasma membrane into
cell cytoplasm from tissue fluid → membrane
depolarized

Na+ gates area at first wide open → K+ area

opened → Na+ are nearly closed again

Action potential - altered polarity due to

sudden influx of Na+. 140mV, with outside
membrane negative to the inside
- very brief, lasting 5msec.
- quickly ceases, and membrane permeability for K+ ion increases

Nerve impulse (AP)

- starts at the initial segment of the axon and is self-propagating wave
- once generated, AP spreads away from initiation site
- Stimulus alters the permeability of membrane to Na+ ions at the point of stimulation → Na+ enters the axon → Positive ions
outside plasma membrane (axolemma) quickly decreases to zero → Membrane potential reduced to zero = Depolarization

After passage of nerve impulse along nerve fiber, while the axolemma is still depolarized, a second stimulus however is strong, is
UNABLE to excite the nerve = Absolute refractory period
WHY? Because of Na+ channels become inactivated, and no stimulation can open Na+ gate

→→ Relative refractory period - this makes continous excitatory state of the nerve impossible and limits the frequency of
impulse

 The greater the strength of the initial stimulus, the larger the initial depolarization and the greater will be the spread
into the surrounding areas of the plasma membrane.
 Summation - result of multiple excitatory stimuli applied to a neuron’s surface

 Conduction velocity of a nerve fiber is proportional to the cross-sectional area of the axon,
- thicker fibers conducting more rapidly than those of smaller diameter.
- In the large motor fibers (a fibers), the rate may be as high as 70 to 120 m/s;
- the smaller sensory fibers have slower conduction rates

Myelinated fibers
+ Myelin sheath - serves as insulator, and few ions
can flow thoufh the sheath
= can only be stimulated at the NODES of RANVIER,
where axon is naked.

SALTATORY CONDUCTION
= AP jumps from one to the next node→ AP at one
node sets up a current in the surrounding tissue fluid
→ depolarizes the next node

 More rapid mechanism than is found in

nonmyelinated fibers (120 m/s) in a large
myelinated fiber
 , 0.5m/s in very small unmyelinated fiber

Nonmyelinated fibers
= AP passes continously along the axolemma,
progressively axciting neighboring areas of
membrane.

Sodium and Potassium Channels

-are formed of protein molecules that extend through full thickness of plasma membrane
- SELECTIVITY OF CHANNEL IS NOT DUE TO DIAMETER OF IONS
- movement of ions in solution depends not only on the size of the ion but also on the size of the shell of water surrounding it.
Nerve Cell Processes
Neurites - processes of a nerve cell - may be divided into dendrites and axon
Dendrites - are short processes of the cell body. Diameter tapers as they extend from cell body and they branch profusely.
Dendritic spines - finer branches bearing large numbers of small projections
During early embryonic development. dendrites are overproduced.. Later, they are reduced in number and size in response to
altered functional demand from afferent axons
Axon - is longest processes of the cell body.
- it arises from a small conical elevation on the cell body, devoid of Nissl granules, called axon hillock
Occasionally, axon arises from proximal part of dendrite.
-tubular and is uniform in diameter; tends to have smooth surface
Terminalis - distal end of terminal branches of axon; often enlarged
Axolemma - plasma membrane bounding the axon
Axoplasm - cytoplasm of axon; lacks Nissl granules and golgi complex.
- site for production of protein, RNA and ribosomes are absent.
Initial segment of axon- is the first 50-100mcm after it leaves the axon hillock of nerve cell body.
- is the most excitable part of the axon and is the site at which an AP originates.

Axon Transport
Anterograde transport - transported from the cell body to the axon terminals
-Fast anterograde transport = 100 to 400 mm/day ; refers to the transport of proteins and transmitter substances
or their precursors.
- Slow anterograde = tramport of 0.1 to 3.0 nmm/day refers to the transport of axoplasm and includes th
microfillaments and microtubules
Retrograde transport - how the cell bodies of nerve cell respond to changes in distal end of axon.
Synapses
- site where two nerurons or a neuron and skeletal muscle of gland cell come into close proximity and functional interneuronal
communivation occurs
- communication is one direction only
- most common type is that which occurs between an axon of one neuron and dendrite or cell body of second neuron
- terminal expansion (bouton terminal) - it appears as axon approaches the synapse

Neurotramitters
- Ach, Norepinephrine, epinephrine, dopamine, glycine, serotonin, GABA, enkephalins, substance P, Glutamic acid
Presynaptic vesicles & mitochondria - play key role in the release of neurotransmitter substance at synapses
Vesicles - contain the neurotransmitter substance that is released into synaptic cleft
Mitochondria - provide ATP for the synthesis of new transmitter substances
Acetylcholine (Ach) - widely used as transmitter by different neurons in CNS and PNS
Dopmine - released by neurons in the substantia nigra,
Glycine - found principally in synapses in the spinal cord

ALL skeletal neuromuscular junctions use only Ach as transmitter

NEUROTRANSMITTER ACTION
All neurotrasmitter are released from their nerve endings by the arrival of the nerve impulse (AP) → influx of Cai+ ions, →
synaptic vesicles fuse with the presynaptlc membrane → neurotransmitters ejected into the extracellular fluid in the synaptic cleft
→ diffuse across the gap to the postsynaptlc membrane → raising or lowering the resting potential of the postsynaptlc
membrane for a brief period of time

Receprtor proteins on postsynaptic membrane binds the transmitter and undergo immediate conformational change → ion
channel gate → generate EPSP or IPSP
Ach - found at the neuromuscular junction, in autonomic ganglia , and at parasympathetic nerve endings
In CNS, motor neuron collaterals to Renshaw cells are cholinergic
In hippocampus, ascending reticular pathways. and the afferent fibers for the visual and auditory systems, the
neurotransmitters are also cholinergic.

Acetylchollneaterue (AChE) - enzyme that the limits destruction of the transmitter in the synaptic cleft

Norepinephrine-ts found at sympathetic nerve endings. I

In the CNS, it is found in high concentration ln the hypothalamus.

Dopamine - found in high concentration in dlfferent parts of the CNS, such as In the basal nuclei (ganglia).

Neuromodulators capable of modulating and modifying the activity of the postsynaptlc neuron
- can coexist with the principal neurotransmitter at a single synapse
- they enhance, prolong, inhibit, or limit the principal neurotransmitter's effect on the postsynaptic membrane
- act through a second-messenger system

Electrical synapse
- are gap junctions containing channels that extend from the cytoplasm of the presynaptlc neuron to that of the postsynaptlc
neuron: They are rare ln the human CNS.

NEUROGLIA
- these are neurons of the CNS are supported. by several varieties of nonexcltable cells
- generally smaller than neurons and outnumber them by 5-10 times
- comprises about half of total volume of brain and spinal cord
- four types of neuroglial cells:
(1) astrocytes (2) oligodendrocytes (3) microglia (4} ependyma