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Degeneration :
After complete transaction of the nerve, the peripheral parts of the axons
undergo certain degenerative changes which are often called Wallerian
degeneration.

Degeneration takes place at three levels :

•In the nerve cell

•In the proximal part of the cut fibre and
•In the distal part of the cut fibre

Degeneration : Change occurring in the proximal part of the axons and also the
cell bodies following section of an axon is known as retrograde degeneration.
The changes in the cell bodies are :

1.Chromatolysis : Nissl granules disappear. It starts within 48 hours and

becomes maximum by 15-20 days.

2.Golgi apparatus, mitochondria and neurofibrils break up and disappear.

•The cell draws in more fluid, swells upP.Deb

and becomes rounded. 3
4. The nucleus is pushed to the periphery. In severe cases it may be totally
extruded, in which case, the nerve cell completely dies and disappears.
The degree of damage and chromatolysis depend on :

a) The distance of lesions from the nerve cell- Lesser the distance greater
will be the damage.
b) Nature of Section : If it is a sharp cut, the effects will be less. But if
forcibly torn, the damage is severe and often the cell dies.

Degeneration in the Proximal part of the cut fibre

Since this part remains connected with the mother cell, degeneration cannot
be complete unless the nerve cell dies. Ordinarily, degeneration proceeds
centrally as far as upto the first node of Ranvier and in most cases
degenerative changes may extend up to a few internodes when
regenerative changes are initiated from the end of the central stump. In
more severe cases, it may proceed to a little higher. The nature of this
degeneration and the subsequent regeneration is same as in the distal
stump or part. Regeneration takes place if the neurone survives.
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Degeneration in the distal part of the cut fibre

Since this part is totally separated from the mother cell, it degenerates
completely. Degeneration starts simultaneously in the whole length of the fibre
up to its terminal arborizations within 24 hours and is completed by 3 weeks.

Following degenerative changes are seen :

Histological Changes :

1.The neurofibrils swell, become tortuous and ultimately disappear and the axis
cylinder breaks up into short lengths.

2.The myelin sheath disintegrates into droplets of fat. Lecithin splits up into
glycerol, phosphoric acid, fatty acid and choline. They are partly removed by
macrophages and partly washed out in the blood stream. If the damage be
inside the central nervous system, no further change takes place.

But if it be in the peripheral nervous system the neurolemma shows the

following changes :
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The nuclei of Schwann cell multiply mitotically and the Schwann cell
cytoplasm increases in amount. It starts 4-9 days after section. The
macrophages penetrate the neurolemmal tubes and remove the debris. The
Schwann tissue gradually fill up the whole tube and the process is completed
by three months. From the cut of the distal end, the proliferating Schwann
tissue spreads upwards toward the central cut end and in this way may bridge
up a considerable gap (even up to 3 cm) between the two cut ends. The rate of
progress of this growth is 1-2 mm per day. The peripheral neurolemmal tube
shrinks to half its original diameter in 7 weeks and may remain so for about 18
months. The above degenerative changes in the distal cut end of the fibres were
first observed by Waller and according to him it is known as Wallerian
degeneration.

Degeneration of Nerve endings :

The framework of both sensory and motor endings can resist degeneration for
months. If the nerve fibre fail to regenerate, the endings also atrophy.

Transneuronal degeneration :
When neurone or its motor fibre degenerates, the neurone next in the chain is
often found to degenerate also. This takes place in spite of the fact that there is
no anatomical continuity through the synapses.
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 It is probably an example of disuse atrophy. In many conditions, this type
of degeneration occurs e.g.,

1. After section of the optic nerve, the cells in the lateral geniculate body
degenerate.

2. After section of the posterior spinal root, the posterior horn cells
degenerate.

3. In lesions of the motor cortex or pyramidal tracts, the anterior horn cells
may degenerate.

This type of degeneration may be the underlying cause of the so-called

System diseases viz., Amyotorphic lateral sclerosis, etc., where
degeneration of anterior horn cells follows that of the pyramidal tracts.

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Regeneration :

Regeneration takes place only outside the central nervous system where
neurolemma is present. Presence of neurolemma is, therefore, essential for the
process. Hence, in the central nervous system, neurolemma being absent, nerve
fibre do not regenerate at all. The following steps are seen during
regeneration :

 The axis cylinder grows from the central cut end as a rounded sprout and
proceeds towards the solid neurolemmal cord. The proliferated Schwann tissue
in the peripheral cut end and its prolongation towards the central cut end
provide an influence which guides the approaching axis cylinder. Each growing
fibre splits up into numerous neurofibrils (even up to 100), the Schwann cells
disappear and the fibrils enter the newly made neurolemmal tube (2-3weeks
after the section, the inner wall of the tube may contain a number of fibrils).
All the fibrils degenerate, excepting a single one, which gradually enlarges and
occupies the central part of the whole length of the tube proceeding
peripherally. The daily rate of growth is about 0.25 mm in the scar tissue
between the two cut ends and 3-4 mm in the peripheral neurolemmal tubes.

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Myelin sheath begins to appear in about 15 days and proceeds peripherally
along the fibre at a slower rate than the growing axis cylinder.

Increase in the diameter of the fibre takes place slowly. The diameter of the
fibre is limited by the size of the neurolemmal tube and that of the parent
nerve cell.

With a clean sharp wound and the cut ends being in apposition, some degree
of recovery usually takes place in 6-24 months. For a motor nerve, recovery
may be complete. But for a mixed nerve, it is rarely so.

In the regenerated fibres the axis cylinder and myelin sheath are reduced in
thickness, the intermodal distance is also diminished. But the rate of
conduction of nerve impulses in the regenerated fibres remains the same.

Complete functional regeneration occurs after histological regeneration- 3

weeks in case of motor nerve fibres and 5 weeks in case of sensory nerve
fibres.

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 PROPERTIES OF SYNAPSE
1. ONE WAY CONDUCTION (BELL-MAGENDIE LAW)

According to Bell-Magendie law, the impulses are transmitted only in one

direction in synapse, i.e. from presynaptic neuron to postsynaptic neuron.

2. THE SYNAPTIC DELAY

During the transmission of impulses via the synapse, there is a short delay
in transmission. It is called the synaptic delay. It is due to the time taken
for :
i. Release of neurotransmitter
ii. Movement of neurotransmitter from axon terminal to post synaptic
membrane.
iii. Action of the neurotransmitter to open the ionic channels in post
synaptic membrane.
The synaptic delay is one of the causes for the latent period of the reflex
activity.
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3. FATIGUE

During continuous muscular activity, the synapse forms the seat of fatigue along
with the Betz cells present in the motor area of the frontal lobe of the cerebral
cortex. The fatigue at the synapse is due to the depletion of neurotransmitter
substance, acetylcholine.
Depletion of acetylcholine occurs by two factors :
i. Soon after the action, acetylcholine is destroyed by acetylcholinesterase.

ii. Due to continuous action, new acetylcholine is not synthesized.

These two factors leads to lack of acetylcholine resulting in fatigue.

4. SUMMATION

When many presynaptic excitatory terminals are stimulated simultaneously or

when single presynaptic terminal is stimulated repeatedly, there is summation or
fusion of effects in postsynaptic neuron, i.e. there is progressive increase in the
excitatory postsynaptic potential. It is called summation. Summation is of two
types :

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i. Spatial Summation :
It occurs when many presynaptic terminals are stimulated simultaneously.

ii. Temporal Summation :

It occurs when one presynaptic terminal is stimulated repeatedly.
Thus, both spatial summation and temporal summation play an important
role in the facilitation of response.

5. ELECTRICAL PROPERTY

The electrical properties of synapse are the EPSP and IPSP.

When action potential causes increased permeability of the postsynaptic

membrane to all ions viz., Na+, K+ and Cl-, then it results in EPSP (Excitatory
post synaptic potential)

When action potential causes selective permeability of the postsynaptic

membrane to K+ ions, then it results in IPSP (Inhibitory post synaptic
potential)
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NEURO-MUSCULAR JUNCTION

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The skeletal muscle fibres are innervated by large, myelinnated nerve fibres
that originate from large motor neurons in the anterior horns of the spinal
cord.

Each nerve ending make a junction, called the neuromuscular junction, with
the muscle fibre near its midpoint. The action potential initiated in the
muscle fibre by the nerve signals travels in both directions toward the
muscle fibre ends.

Physiologic antomy of the neuromuscular junction- The motor

end plate

The neuromuscular junction form a large, myelinated nerve fibre to a

skeletal muscle fibre. The nerve fibre forms a complex of branching nerve
terminals that invaginate into the surface of the muscle fibre but lie outside
the muscle fibre plasma membrane. The entire structure is called the motor
end plate. It is covered by one or more Schwann cells that insulate it from
the surroundings fluids.

 The invaginated membrane of the muscle fibre membrane is called the

synaptic gutter or synaptic trough. P.Deb 15
 The space between the terminal and the fibre membrane is called the
synaptic space or synaptic cleft. This space is 20-30 nm wide.

At the bottom of the gutter are numerous smaller folds of the muscle
membrane called subneural clefts, which greatly increase the surface area at
which the synaptic transmitter can act.

In the axon terminal numerous mitochondria supply ATP for the
synthesis of neurotransmitter acetylcholine.

The acetylcholine inturn excites the muscle fibre membrane. Acetylcholine

is synthesized in the cytoplasm of axon terminals but are absorbed rapidly
in to many small synaptic vesicles about 300,000 in the terminal of a single
end plate.

In the synaptic space are large quantities of the enzyme acetylcholine
esterase, which destroys acetylcholine in a few milliseconds after it has been
released from the synaptic vesicles.

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Mechanism of transmission of nerve impulse across the
neuromuscular junction

 When a nerve impulse reaches the neuromuscular junction, about 125

vesicles of acetylcholine is released from the terminals into the synaptic space.

On the inside surface of the neural membrane are linear dense bars. To
each side of each dense bar are protein particles that penetrate the neural
membrane, these are voltage gated calcium channels.

When action potential spreads over the terminals, these channels open and
allow calcium ions to diffuse from the synaptic space to the interior of the
nerve terminal. The calsium ions, in turn, are believed to exert an attractive
influence on the acetylcholine vesicles, drawing them to the neural membrane
adjacent to the dense bars. The vesicles then fuse with the neural membrane
and empty their acetylcholine into the synaptic space by the process of
exocytosis.

At the neck of the subneural clefts there exists the acetylcholine receptors in
the muscle fibre membrane.
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These are acetylcholine-gated ion channels, and they are located almost
entirely near the mouths of the subneural clefts lying immediately below
the dense bar areas, where acetylcholine is emptied into the synaptic space.

 The receptor is a protein complex(MW-275,000), the complex is

composed of five subunits proteins, two alpha proteins and one each of
beta, delta, and gamma proteins. These protein molecules penetrate all the
way through the membrane , lying side by side in a circle to form a tubular
channel.

The channel remains constricted until two acetylcholine molecules

attach respectively to the two alpha subunit proteins . This causes a
conformational change that opens the channel.

The opened acetylcholine channel has a diameter of 0.65 nm, which is

large enough to allow the important positive ions – Na +, K+ and Ca++ to
move easily through the opening.

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 Whereas the negative ions such as Cl- ions cannot pass through because
of strong negative charges in the mouth of the channel that repel these
negative ions.

In practice far more Na+ ions move through the acetylcholine channels
than any other ions due to two reasons :
1.The extracellular concentration of Na+ ions is more , and
2.The inside is electronegative (-70 to -90mV) which easily allows the Na + ions
to enter and at the same time prevents the efflux of the K+ ions to outside.

This creates a local positive potential change inside the muscle fiber
membrane, called the end-plate potential.

In turn, this end plate potential initiates an action potential that spreads
along the muscle membrane and thus causes muscle contraction.

The acetylcholine, once released into the synaptic space , continues to

activate the acetylcholine receptors as long as the acetylcholine persists in the
space.
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Acetylcholine Receptor

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 Acetylcholine is removed by two means-

1. Most of the acetylcholine is destroyed by the acetylcholinesterase

enzyme present in the synaptic space remains attached to the fine
connective tissues.

2. A small amount of acetylcholine diffuses out of the synaptic space and is

then no longer available to act on the muscle fibre membrane.

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What is Reflex ?

It is the involuntary or autonomic response elicited by specific stimulus of

threshold intensity with the involvement of CNS.

Reflex Arc :

It is the pathway through which any reflex action is mediated.

The Components of reflex arc are as follows :

i.Receptor : This detects the change of internal or external environment and

transmits the impulse to center.
ii.Afferent (sensory) nerve- It carries the impulse from receptor to center.
iii.Higher centers- It is the part of CNS where afferent limb ends and either
synapses directly with efferent motor neuron or establish connection with the
efferent neuron via interneurones.
iv.Efferent (Motor ) nerve- It carries the efferent impulses from the centre to the
efferent organ.
v.Efferent organ – These are basically muscles or glands which shows the reflex
action.
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Classification of reflexes :

a.Depending on inborn or acquired : It is of two types-

i. Unconditioned reflex : These reflexes are present since birth i.e. inborn.

Example : Salivation after taking food, knee jerk etc.

ii. Conditioned reflex : These are not present from birth but acquired in later life on
the basis of past experiences through conditioning and learning.
Example : Salivation by seeing tasty food the taste of which is known.

b. Depending on the number of synapses present in the reflex arc :

It is of two types :
i.Monosynaptic reflex :

When there is only one synapse present in the reflex arc it is known as
monosynaptic
reflex. Example : Knee jerk, Ankle jerk etc.
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ii. Polysynaptic reflex :
When more than one synapse is present in the reflex arc it is known as
polysynaptic reflex.
Example : Withdrawl reflex i.e., protective reflex e.g. automatic withdrawl
of limb if it comes in contact with hot object.

C. Physiological Classification : It is of two types :

i. Extensor reflex :
These reflexes are responsible for extensor movement of limbs at joints.
Stretch reflexes are extensor reflexes. These are responsible for muscle tone
and posture.

ii. Flexor reflexes : These are reflexes which cause flexion of the joints in
response to nociceptive (pain) stimuli. Withdrawl reflexes are the example
of flexor reflex.
D. Functional classification : are of two types-

i. Somatic reflex : It involves the somatic nervous system. Example- Knee jerk
ii. Autonomic reflex : It involves the autonomic nervous system. Example- Sino-
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E. Clinical Classification : It is of four types :

i. Superficial reflexes : These are initiated by stimulating appropriate receptors

of skin and mucous membrane. These are usually polysynaptic. Example :
Planter reflex, corneal reflex etc.
ii. Deep reflexes : These are elicited on stroking the tendon. These are basically
stretch reflexes. Example : Knee jerk, ankle jerk etc.
iii. Visceral reflexes : These are reflexes in which part of the reflex arc is formed
by autonomic nervous system. Example- Papillary reflex, Carotid sinus reflex
etc.

iv. Pathological reflexes : These are not found normally. Elicited in case of
diseased state.

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Reflex Action :
Reflex action is an involuntary effector response due to a sensory stimulus.
It is the basic physiological unit of integration in the neural activity.

Unconditioned Reflex : Unconditioned reflexes are inborn. The nerve paths

are fixed from the very birth. Any material alteration is considered as
disease. Hence, examination of reflexes is a great help in the diagnosis of
various diseases.

Conditioned Reflex : The conditioned reflexes are acquired after birth. Such
reflexes need previous learning, training, or conditioning. The example is
the secretion of saliva by the sight, smell, thought or hearing of a known
edible substance.

Cerebral cortex is responsible for the establishment of conditioned reflexes

through the development of new connection with different subcortical
centres. For establishment of conditioned response or reflex through specific
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conditioned stimuli, specific cortical and subcortical centres are
responsible for its development. As for example, for the production of
conditioned salivation reflexes, the cortical taste centres as well as the
visual and auditory areas along with its subcortical centres are responsible
if the conditioned stimulus are the ringing of bell and giving of food.

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THANK YOU

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