1 the nervous system

1 DAWN V TO MY M.Pharm., Asst. Professor, Dept. of Pharmacology, ST.JOSEPH’S COLLEGE O F PHARMACY, CHERTHALA.

THE NERVOUS SYSTEM

It is a highly organized network of billions of neurons and numerous neuroglias.

Structure of nervous system:

It consists of the brain, cranial nerves and their branches, the spinal cord, the spinal nerves,

ganglia, enteric plexuses and sensory receptors.

Histology of nervous tissue:

Nervous tissue is made up of two types of cells. They are

1. Neurons and

2. Neuroglia.

1. Neurons: They have the property of electrical excitability (the ability to produce action potentials or

impulses in response to stimuli). Its functions are:

a. Sensing

b. Thinking

c. Remembering

d. Controlling muscle activity and

e. Regulating glandular secretions.

2. Neuroglia: They support, nourish and protect the neurons. It also maintains homeostasis of the fluid

nourishing neurons.

Parts of a neuron:

The typical neuron has 3 main parts. They are:

1. A cell body.

2. Dendrites and

3. An axon.

1. Cell body contains nucleus and cytoplasm with cell organelles like lysosomes, mitochondria,

Golgi complex, Nissl bodies (clusters of rough endoplasmic reticulum which are sites of protein

synthesis used for replacement, growth and regeneration). The cytoskeleton (provide support

and shape) contains neurofibrils and microtubules. The 2 processes/extensions arising from

the cell body of a neuron are the multiple dendrites and axons.

2. Dendrites (tree like): It is the receiving/input portion of a neuron; they are mainly connected to

receptors for receiving stimuli. Its cytoplasm contains Nissl bodies, mitochondria and other

organelles.


3. Axon: It propagates nerve impulses to another neuron/a muscle fiber/a gland cell. An axon

contains mitochondria, microtubules, and neurofibrils. It has no rough endoplasmic reticulum

and hence no protein synthesis. Its structure includes:

a) Axon hillock: It is a cone shaped elevation at which axon connects to the cell body.

b) Initial segment: It is the first segment of the axon arising from cell body.

c) Trigger zone: It is the junction between axon hillock and initial segment.

d) Axoplasm: It is the cytoplasm of an axon.

e) Axolemma (sheath/husk): It is the plasma membrane covering axoplasm.

f) Neurolemma: It is the outer cytoplasmic layer of the Schwann cell, which encloses the

myelin sheath. It aids regeneration of injured axon.

g) Nodes of Ranvier: It is the gap in the myelin sheath which appears at intervals along the

axon.

h) Axon collaterals: It is the branches of the axon arising at right angles to the axon.

i) Axon terminals: Axon and axon collaterals divides into fine process called axon terminals.

j) Synaptic end bulbs: The axon terminals swell into bulb shaped structures known as synaptic

end bulbs.

k) Varicosities: Some axon terminals have strings of swollen bumbs called varicosities.

l) Synaptic vesicles: They are tiny membrane bound sacs which stores neurotransmitter

(chemicals).


m) Synapse: It is the site of communication between two neurons/between a neuron and an

effector cell.

n) Neurotransmitters: They are chemicals/hormones released throughout the body from

synaptic vesicles of neuron for communication, when released into synaptic cleft they

excite/inhibit other neurons/muscle fibers/gland cells. E.g. Acetylcholine, amino acids:

glutamate and aspartate have powerful excitatory action in CNS, Gamma aminobutric acid

(GABA) and glycine have important inhibitory action in CNS. Biogenic amines:

Norepinepherine, epinephrine, dopamine, serotonin or 5-Hydroxytryptamine (5-HT), ATP

and other purins: Adenosine, ATP, ADP and AMP have excitatory action in both CNS and

PNS, nitric acid have vasodilator effect on blood vessels. Neuropeptides: Substance P,

enkephalins, endorphins, dynorphins, hypothalamic releasing and inhibitory hormones,

angiotensin II, cholecystokinin.

o) Synaptic cleft: The space between neurons at a nerve synapse across which a nerve impulse

is transmitted by a neurotransmitter called also synaptic gap.

p) Ganglia: ___________

Different types of neurons:

1. Multiple neurons: They have several dendrites and one axon. E.g. neurons in the brain and

spinal cord.

2. Bipolar neurons: They have one main dendrite and one axon. E.g. Neurons in retina of eye, in

the inner ear and in olfactory area of the brain.

3. Unipolar neurons: The dendrites and axon fused into a single process that divides into 2

branches a short distance from the cell body. E.g. sensory neurons of touch/stretch.

Neuroglia (Glue): They are smaller (than neurons), more numerous than neurons. They mature, divide

and fill the spaces occupied by neurons which may be damaged or injured. Brain tumors derived from

glia are known as gliomas (highly malignant).

There are 6 types of neuroglia. Four are found only in the Central Nervous System (CNS).

1. Astrocytes,

2. Oligogendrocytes,

3. Micorglia and

4. Ependymal cells.

The remaining 2 types:

1. Schwann cells

2. Satellite cells are present in the Peripheral Nervous System (PNS).


Central Nervous System:

1. Astrocytes: They are star shaped with many processes.

Functions:

It maintains appropriate chemical environment for generation of nerve impulses.

Provide nutrients to the neurons.

Takes up extra/excess neurotransmitters released.

Helps in the migration of neurons during brain development.

Helps in the formation of Blood Brain Barrier (BBB).

2. Oligogendrocytes (tree like): They are smaller than astrocytes with fewer processes with round

or oval cell body.

Functions:

It forms supporting network around CNS neurons.

It produces myelin sheath around adjacent axons of CNS neurons.

3. Micorglia (small): Small cells with few processes derived from mesodermal cells that also give

rise to monocytes and macrophages.

Functions:

It protects CNS cells from diseases by engulfing invading microbes.

Migrate to areas of injured nerve tissue where they clear away debris of dead cells (may

also kill healthy cells)

4. Ependymal cells (epen – above, dym - garment): Epithelial cells arranged in a single layer,

range in shape from cuboidal to columnar, and may be ciliated/nonciliated.

Functions:

It lines the ventricles of the brain and central canal of the spinal cord (spaces filled with

CSF).

It helps in the formation of Cerebrospinal Fluid (CSF) and assists in its circulation.

Peripheral Nervous System (PNS):

1. Schwann cells: They are flattened cells that encircle PNS axons.

Functions:

Each cell surrounds multiple unmyelinated axons with a single layer of its plasma

membrane or produces part of the myelin sheath around a single axon of a PNS neuron.

Participate in regeneration of PNS axons.


2. Satellite cells: Flattened cells arranged around the cell bodies of neurons in ganglia.

Functions:

Support neurons in PNS ganglia.

Myelination: Multilayered lipid and protein covering produced by neuroglia called myelin sheath

electrically insulates the axon of a neuron and increases the speed of nerve impulse conduction.

Neurons which have myelination are called myelinated neurons and without myelination are called

unmyelinated neurons. The amount of myelin increases from birth to maturity. It increases the speed of

nerve impulse conduction.

Two types of neuroglia produce myelin sheath, i.e. Schwann cells in the PNS and

Oligodendrocytes in the CNS.

Gray and white matter:

White matter: It is due aggregations of myelinated and unmyelinated axons of many neurons.

Gray matter: It contains cell bodies, dendrites, unmyelinated axons, axon terminals and

neuroglia. It looks grayish because of Nissl bodies and absence of myelin.

Functions of nervous system:

1. Sensory function: Detection of internal (blood acidity) and external (touch/smell etc.) stimuli.

The sensory/afferent neurons carry information from cranial and spinal nerves into the brain

and spinal cord.

2. Integrative: It process the information received, analyze and store the information for giving

appropriate responses. The interneurons process the information. They have short axons and

contact nearby neurons in the brain, spinal cord/a ganglion. Most of the neurons in the body are

interneurons.

3. Motor function: It is the response to the processed information. The motor neuron/efferent

neuron carries the response information from the brain towards the spinal cord/out of the brain

and spinal cord to the cranial/spinal nerves known as effectors.

Functional classification (based on direction of nerve impulse)

1. Sensory or afferent neurons: They have sensory receptors in the dendrites of sensory neurons

forms action potential which is conveyed into the CNS through cranial/spinal nerves. They are

mostly unipolar in structure.

2. Motor or efferent neurons: They convey action potential away from the CNS to effectors

(muscles and glands) in the PNS through cranial and spinal nerves. They are mostly multipolar in

structure.


3. Interneuron or association neurons: They are found in the CNS in between sensory and motor

neurons. It integrates (process) incoming sensory information from sensory neurons and then

triggers a motor response by activating the neurons. They are mostly multipolar in structure.

Organization of the nervous system

I. Central Nervous System (CNS): It consists of the brain and spinal cord. It controls all the

activities of the body and also the source for thoughts, emotions and memories.

II. Peripheral Nervous System (PNS): It consists of all the nerves outside the CNS and includes

cranial nerves and their branches, spinal nerves and their branches, ganglia and sensory

receptors. It is classified into

1. Somatic Nervous System (SNS, somat-=body): It consists of (a) sensory neurons that

convey information from somatic receptors in the sense organs, head, body wall and limbs

to the CNS and (b) motor neurons that conduct impulses from CNS to skeletal muscles and

is voluntary.

2. Autonomic Nervous System (ANS, auto-=self, -nomic=law): It consists of (a) sensory

neurons that convey information from autonomic sensory receptors in the visceral organs

(internal organs) to the CNS and (b) motor neurons that conduct nerve impulses from CNS

to smooth muscles, cardiac muscles and glands and is involuntary. The motor part of the

ANS consists of 2 branches: (i) The sympathetic nervous system and (ii) The

parasympathetic nervous system. The 2 divisions have opposing action e.g. sympathetic

neurons increase heart rate and parasympathetic neurons decreases heart rate.

3. Enteric Nervous System (ENS, enter-=intestine): It supplies to the GI (Gastrointestinal

tract) tract and is involuntary. It consists of (a) sensory neurons of the ENS monitor changes

within the GI tract and stretching of its walls and convey the information to the CNS and (b)

motor neurons contracts GI tract smooth muscle to propel food through the tract and helps

in the secretions of GI tract organs such as acid in the stomach, enzymes and hormones

from the exocrine and endocrine glands.


ION CHANNELS:

They are channel proteins present in the plasma membrane; when open it allows the movement

of specific ions across the plasma membrane based on their electrochemical gradient (charge and

concentration). The movement of ions creates a flow of electrical current which changes the membrane

potential. The channels will open or close due to the presence of gates.

Types of ion channels in the plasma membrane

There are 4 types of ion channels

a. Leakage channels: There are 2 types of leakage channels in the plasma membrane. The sodium

leakage channels are less than potassium leakage channels and hence the membrane

permeability to potassium ion is higher than sodium ion permeability. The gates of leakage

channels randomly alternate between open and closed positions.

b. Ligand gated channels: The gates of the ion channels opens or closes in response to specific

chemicals. The chemical ligands include neurotransmitters, hormones and ions e.g.

Neurotransmitter acetylcholine opens cation channels and allow sodium and calcium influx and

potassium out flux.


c. Mechanically gated channels: The gates of the ion channels opens or closes in response to

mechanical stimulation in the form of vibrations (sound), touch, pressure or tissue stretching

etc. e.g. the auditory receptors in the ear monitor stretching of diaphragm and opens or closes

the ion channels.

d. Voltage gated channels: The gates of the ion channels opens or closes in response to change in

membrane potential (voltage). Voltage gated channels participate in the generation and

conduction of action potential.


Resting membrane potential:

The resting membrane potential is the charge exhibited by the membrane of the excitable cell at

rest. It exists because the inside of the cell is negative due to the charge of the phosphates and amino

acids in proteins. The potential varies from -40 to -90 according to the cells. Usually it will be -70 mV.

The minus sign denotes that the inside of the cell is negative to outside the cell. The cell exhibiting

membrane potential is polarized.

Factors contributing to resting membrane potential:

1. Unequal distribution of ions in the Extracellular Fluid (ECF) and cytosol: Extracellular fluid

rich in sodium and chloride ions and the cytosol is rich in potassium ions.

2. Inability of most anions to leave the cell: The anions inside the cell are attached to non-

diffusible molecules such as ATP and large proteins.

3. Electrogenic nature of the Na+ /k+ ATPases: These pumps help to maintain resting

membrane potential by pumping out Na+ and pumps in k+. The pumps expel 3 Na+ in

exchange of 2 k+ and this contribute to the negativity of the resting membrane potential.

Graded potential generation:

The graded potential is a small change in the membrane potential making it either more

polarized (inside of the cell more negative) known as hyperpolarizing graded potential or less polarized

(inside of the cell less negative) known as depolarizing graded potential.


It occurs when stimulus opens or closes mechanically gated or ligand-gated channels present in

the dendrites of sensory neurons. It occurs mainly in the dendrites and cell body of a neuron. They are

called graded because they vary in their amplitude depending on the strength of the stimulus. They die

out by decremental conduction as they spread along the membrane. They are useful for short distance

communication only. Graded potential add together by summation.

Action potential generation:

The action potential (AP) is a big and rapid change in the membrane potential that which can

produce an action. An action potential occurs in the membrane of the axon of a neuron when the

depolarization reaches threshold (-55mV). A sub-threshold stimulus cannot produce an action potential.

It has 2 main phases:

1. Depolarizing phase: An impulse on reaching the pre-synaptic nerve ending opens the voltage-

gated Ca2+ channels and triggers the release of neurotransmitter from the synaptic vesicles by

exocytosis. The released neurotransmitter binds to the ligand-gated ion channel receptors and

opens the Na+ channels producing depolarizing graded potential. When it reaches threshold

voltage-gated Na+ channels open rapidly facilitating the influx of Na+ by the electrical and

chemical gradient. This sudden influx of Na+ changes the membrane potential from -55 mV to

+30 mV. At peak potential the inside of the membrane is 30 mV more positive than the outside.


Voltage-gated Na+ channel has 2 gates, the activation gate and inactivation gate. At resting state

the inactivation gate is open but activation gate is closed and Na+ ions cannot move inside. At

threshold voltage-gated Na+ channels are activated and both activation and inactivation gates

are opened and influx of Na+ ions begins. As a result the membrane depolarizes further

resulting in opening of more and more voltage-gated Na+ channels by positive feedback

mechanism to reach +30 mV.

2. Repolarizing Phase: After depolarizing phase the activation gates in the voltage-gated Na+

channel opens and closes the inactivation gates rendering the channel in an inactivated state.

The threshold depolarization also opens the voltage-gated K+ channels but they open more

slowly and happen about the same time the voltage-gated Na+ channels are closing. The slower

opening of voltage-gated K+ channels and closing of the Na+ channels produce the

repolarization phase of the action potential. Na+ channels are inactivated and the voltage-gated

K+ channels opens accelerating the outflow of K+ ions. This leads to change in membrane

potential from +30 mV to -70 mV. Repolarization allows inactivated Na+ channels to come to

resting state.

After-hyperpolarizing phase: At repolarization phase outflow of K+ ions may be large to cause an

after-hyperpolarizing phase of the action potential. The voltage-gated K+ channels remain open and the

membrane potential becomes more negative (-90 mV). Voltage-gated K+ channels will close and the

membrane potential returns to resting membrane potential (-70 mV).

Refractory period: The period of time after an action potential begins during which an excitable cell

cannot generate another action potential in response to a normal threshold stimulus is called the

refractory period.

Absolute refractory period: During Na+ channel activation and inactivation even a very strong

stimulus cannot initiate a second action potential and this period is defined as absolute refractory

period.

Relative refractory period: It is the period at which a second action potential could be initiated with a

larger stimulus. It is the period at which voltage-gated K+ channels are still open after inactivated Na+

channels have returned to their resting state.

All-or-none principle: An action potential is generated when there is a threshold stimulus and does not

form when there is a sub-threshold stimulus. When an action potential is generated it completely occurs

after threshold stimulus. If it is sub-threshold stimulus an action potential is not at all generated. This

characteristic of an action potential is known as the all-or-none principle.

Propagation of action potentials:

In order to communicate information from one part of the body to another, the action potential has to

travel from the trigger zone to the axon terminal; which is known as propagation of action potential.

There are 2 types of propagation:


1. Continuous conduction: It involves step-by-step depolarization and repolarization of each

adjacent segment of the plasma membrane, as the ions flows through their voltage-gated

channels in each adjacent segment of the membrane. This occurs in unmyelinated axons in

muscle fibers.

2. Salutatory conduction: It occurs in the myelinated axons due to the uneven distribution of

voltage-gated channels. There are only few voltage-gated channels at the place where the

myelin sheath covers the axolemma, and at the node of Ranvier the axolemma has many

voltage-gated channels. Hence current flows across the membrane mainly at the nodes. Current

flows through the extracellular fluid surrounding the myelin sheath and through the cytosol

from one node to next. The flow of current across the membrane occurs only at the node of

Ranvier.

Factors affecting the speed of propagation:

The factors are:

1. Amount of myelination: Action potentials propagate more rapidly along myelinated axons than

along unmyelinated axons.

2. Axon diameter: larger diameter axon propagates action potentials faster than smaller ones due

to their larger surface areas.

3. Temperature: The speed of action potential propagation lowers when cooled.

Presynaptic neuron, postsynaptic neuron, presynaptic potential and postsynaptic potential.

The neurons sending signals (impulses) are called the presynaptic neuron and the potential is known as

presynaptic potential. The neurons receiving the signals (impulses) are called postsynaptic neuron and

the potential generated in the postsynaptic neuron is known as postsynaptic potentials. The post

synaptic potentials are of 2 types:

a. EPSP: It facilitates the release of excitatory neurotransmitters if it reaches threshold and greater

than the inhibitory effects.

b. IPSP: It facilitates the release of inhibitory neurotransmitters if it reaches threshold and greater

than the excitatory effects.

Removal of neurotransmitter:

The removal of neurotransmitter from the synaptic cleft after action potential generation is necessary

for normal synaptic function. The removal of neurotransmitter from synaptic cleft by three ways:

1. Diffusion: The neurotransmitter molecules diffuse away from the synaptic cleft and taken back

to synaptic vesicles.

2. Enzymatic degradation: The neurotransmitters are inactivated through enzymatic degradation.

E.g. enzyme acetyl cholinesterase breaks down acetylcholine in the synaptic cleft into acetate

and choline which are reused.

3. Uptake by cells: the neurotransmitters are actively transported back into the neuron that

released them (reuptake). Some are transported into the neighboring neuroglia (uptake). The


membrane proteins that facilitate uptake are called neurotransmitter transporters. E.g.

neurotransmitter norepinephrine is up taken by the cells.

Synapses

1. Electrical synapse: Action potential (impulses) conduct directly between adjacent cells through

structures called gap junctions containing tubular connexons acting like tunnels to connect the

cytosol of the 2 cells directly. The movement of ions from one cell to next results in the

spreading of the action potential from cell to cell. E.g. Synapses found in the visceral smooth

muscle, cardiac muscle and CNS.

Advantages of electrical synapses:

a. Faster communication – Electrical synapses are faster than chemical synapses.

b. Synchronization – Electrical synapses can synchronize (coordinate) the activity of a group

of neurons or muscle fibers. E.g. Cardiac muscle in heart beat and visceral smooth muscle

move food through the gastrointestinal tract.

2. Chemical synapse: The plasma membranes of the presynaptic and postsynaptic neurons in the

chemical synapse are close but they don’t touch. It leaves a gap of 20-50 nm called synaptic

cleft which is filled with interstitial fluid. As the impulse arrives at the presynaptic nerve ending

it opens the voltage gated Ca2+ channels resulting in Ca2+ influx. It in-turn results in the

exocytosis of the synaptic vesicles releasing neurotransmitters into the synaptic cleft. The

neurotransmitter molecule diffuses across the synaptic cleft and bind to the neurotransmitter

receptors in the postsynaptic neuron’s plasma membrane. Binding of the neurotransmitter to

their receptors on ligand-gated channels opens the channels and allows influx of the particular

ions. Influx of ions changes membrane voltage and postsynaptic potential resulting in

depolarization or hyperpolarization based on the ion channels activated. E.g. opening of Na+

channels allows influx of Na+ which results in depolarization and opening of Cl- channels

allows inflow of Cl- ions resulting in hyperpolarization.

Comparison of graded potentials and action potentials in neuron

1 the nervous system

Education

axon terminals

axon hillock

cell body

h axon collaterals

regeneration of injured

cell organelles

schwann cell

effector cell