Basics of Nervous System

The functions of the cells of the animal body are coordinated by two control systems;
the endocrine system and the nervous system. Endocrine system coordinates functions of
different cells in a slower manner by a collection of blood-borne messengers called hormones.
Nervous system is a rapid control system. Together both the systems regulate most of the internal
functions as well as organize and control the animal behaviour. The nervous system in organisms
is composed of trillions of nerve cells (neurons) distributed throughout the brain, spinal cord, and
peripheral organs in a circuit. These neurons of the body communicate with each other by
electrical and chemical signals to coordinate the functions of internal organs, movement and
sensation and maintain homeostasis.
The different parts of the nervous system throughout the body are interconnected. But for
convenience the whole system is subdivided into a central nervous system (CNS) and a
peripheral nervous system (PNS). CNS includes brain and spinal cord. PNS provides interface
between the CNS and environment. PNS includes the nerves that extend between the brain or
spinal cord and the body’s muscles, glands, and sense organs. PNS includes a sensory component
and a motor component. The sensory component consists of a sensory receptor and afferent
neuron. The motor component comprises of somatic motor fibres, autonomic motor ganglia and
autonomic motor fibres. The autonomic nervous system (ANS) consists of sympathetic,
parasympathetic and enteric nervous system.
The individual nerve cells known as neurons are the basic units of the nervous system.
Neurons of body occur in a wide variety of sizes and shapes. Neurons operate by generating
electrical signals that move from one part to another part of the same neuron or to neighbouring
neurons. Most neurons have a cell body (soma) and two elongated processes called dendrites
and axon. Neuron’s cell body/soma contains the nucleus, mitochondria, Golgi apparatus,
endoplasmic reticulum and ribosomes and thus possesses the genetic information and protein
synthesis machinery. The dendrites are highly branched outgrowths of the cell body which
along with the cell body receive the inputs from other neurons. The branched dendrites increase
the cell’s surface area that increases the neuron’s capacity to receive signals from many other
neurons. As a general rule the dendrites convey impulses/ signals towards the soma.
The axon is a single long process that extends from the cell body. The portion of the axon
close to the cell body and the part of the cell body where the axon is originated is known as the
initial segment or axon hillock. The axon hillock is the “trigger zone” where the electrical
signals are generated. These signals then propagate away from the cell body along the axon. The
main axon may have branches called as collaterals. Near ends, the main axon and its collaterals
undergo further branching to increase neuron’s sphere of influence. Each branch ends in an axon
terminal/ terminal knob/ terminal button. Most of the neurons release chemical messengers,
called neurotransmitters at terminal button to communicate with other cells. Some neurons
release their neurotransmitters from a number of bulged areas along the axon known as
varicosities. Delicate threads like structures called neurofibril are present in neurons from
terminal ends of dendrites to terminal end of the axon. Neurofibrils form a network in the cell
body. Neurofibrils and neurotubules help in transportation of chemicals synthesized in soma to
axon terminals. The process of such transportation is called axonal transport. In general the
axons convey the impulses away from the soma.
According to the number, origin and arrangement of their processes neurons are
classified into as follows:
i. Unipolar neurons: It has a single process called a neurite which after its origin from
soma divides into two branches to function as dendrite and axon. These types of
neurons are found in CNS of invertebrates.
ii. Pseudounipolar neurons: These neurons develop as bipolar neurons with two
processes from soma, but initial segments joins to form a T junction which looks like a
unipolar neuron. These neurons are sensory in nature. Axonal process receives and
transmits the information. These are found in sensory ganglias of cranial nerves of
both vertebrates and invertebrates.
iii. Bipolar neurons: Bipolar neurons have two distinct processes; an axon and a
dendrite, extending from cell body. Such neurons are mostly found in retina and
olfactory epithelium.
iv. Multipolar neurons: Multipolar neuron has the highest number of processes
 extending from cell body. Only one of these processes is axon and others are branching
dendrites. Examples: motor neurons in the ventral grey columns of spinal cord.
v. Anaxonic neurons: These neurons either lack axon (unipolar brush cells) or have an
axon that is indistinguishable (undifferentiated anaxonic neuron) from its dendrites.
These are found in olfactory system of mammals, visual system of human beings.
These neurons release graded potential to influence neighbouring neurons.
Besides neurons, nervous system also contains other type of cells which support and
protect neurons. These cells are known as glial cells or neuroglia. Glial cells are found in both
CNS and PNS. Glial cells provide physical and chemical support to neurons, maintain
homeostasis in nervous system. These cells are also known as ‘glue’ of the nervous system.
Glial cells of CNS:
i. Astrocytes: Most common type of glial cells in CNS. These cells have many
projections which make them look star shaped. There are two types of astrocytes;
protoplasmic astrocytes (have thick projections with many branches) and fibrous
astrocytes (have long slender projections with few branches). Protoplasmic astrocytes
are found in grey matter and fibrous astrocytes in white matter. Astrocytes are mostly
attached to blood vessels supplying CNS and forms part of blood-brain barrier.
Besides part of blood-brain barrier these cells regulate neurotransmitter
(neurotransmitters hang around until an astrocyte recycle them), clean up the dead
+
neurons and K , regulate the blood flow to the brain, synchronize the activity of
axons and regulate the brain metabolism (by storing sugar) and homeostasis.
Dysfunction of astrocytes leads neurodegenerative diseases like Parkinson’s disease,
Huntington’s disease.
ii. Oligodendrocytes: Oligodendrocytes generated from neural stem cells. These spikey
ball shaped cells wrap around the axons of nerve cells to form a protective layer
known as myelin sheath. The sheath is not continuous, but with gaps in between each
membrane called as ‘node of Ranvier’. The nodes help in faster and efficient
transmission of electrical impulses along axons in brain. Oligodendrocytes can be
damaged by the neurotransmitter glutamate at high levels.
iii. Microglia: Also known as microcytes are tiny glial cells and act as brain’s immune
system. Microglias play housekeeping role in learning, and associated with brain
plasticity. They also detect unnecessary synapses and prune them.
iv. Ependymal cells: Ependymal cells forms thin membrane lining the central canal of
the spinal cord, and ventricles. These cells produce cerebrospinal fluid (CSF) and
forms part of blood-brain barrier. The cells have cilia whose movement helps in
circulation of CSF.
v. Radial glia: These cells believed to be a type of stem cell which creates other types of
cells during brain development. During this period radial cells provide scaffolding for
developing neurons. In later life, radial cells help in brain’s ability to change and
adapt.
Glial cells of PNS:
i. Schwann cells: Named after its discoverer ‘Theodor Schwann’. These cells are similar
to oligodendrocytes of CNS by providing myelin sheath around axons. These cells
are also part of PNS’s immune system.
ii. Satellite cells: These cells surround certain neurons with several satellites forming a
sheath around the cellular surface. Some scientists believe these cells are similar to
astrocytes of CNS. Satellite cells make cluster of neurons known as ganglia in ANS
and sensory system. They also help in maintenance of homeostasis in PNS.
Neurogenesis:
Neurogenesis is the process of development of the neurons or glial cells from neural
stem cells (NSC). NSCs include neural epithelial cell, radial glial cells, basal progenitor cells
and intermediate neuronal precursors, subventricular zone astrocytes and subgranular zone radial
astrocytes. During embryogenesis CNS is developed from the neural tube. CNS contains NSCs
from which neurons developed later. The early neural stem cells are known as neuroepithelial
cells (NECs). NECs within a short period of time adopt radial elongated shaped cells which are
called as radial glial cells (RGCs). RGCs are the primary stem cells of mammalian CNS. Then
RGCs proliferate rapidly. Following proliferation phase RGCs undergo cell division to produce
either intermediate neuronal precursors which divide one or more times to produce neurons or
neurons produced directly. Then formed neurons migrate to their designated sites where they
mature and generate neural circuit. After reaching the designated site, these newly formed
neurons sends out processes that will become its axon and dendrites. An enlargement known as
the growth cone forms the tip of each extending axon which helps in finding the correct route
and final target for the process. As the axon grows, its route is guided along the surfaces of glial
cells influenced by several biomolecules like cell adhesion molecules present on surface of glial
cells and newly formed neurons, and some soluble nerve growth factors (NGFs) present in the
extracellular fluid surrounding the growth cone or its target. Once the target of growth cone is
reached, synapses are formed. The synapses are active before their final maturation. Alcohol and
other drugs, radiation, malnutrition, and viruses can cause damage to early stages of neural
development during pregnancy which may lead to permanent damage to the developing fetal
nervous system. Many of the newly formed neurons (50 - 70% in some region) and synapses
degenerate normally due to unknown reasons. The creation and removal of synaptic contacts
begin during fetal development and continue at a slow pace throughout life depending on
growth, learning, and aging. Division of neuronal stem cells is completed before birth. If
growing axons are severed during prenatal life, they can repair themselves by giving rise to a
new growth cone.
Synapse
A synapse is a specialized anatomic junction between two neurons, at which the electrical
activity in presynaptic neuron influences the electrical/metabolic activity in the postsynaptic
neuron. Synapses include parts of the presynaptic and postsynaptic neurons and the extracellular
space between these two neurons. Here the neurons are connected functionally. Approximately
14
10 number of synapses is present only in the CNS. Synapses are of different types depending on
how the connections between neurons are established, Ex. axo-dendritic, axo-somatic and axo-
axonic. Most synapses are either of axo-dendritic or axo-somatic.
Functionally, synapses are of two types; electrical and chemical. At electrical synapse,
the plasma membranes of the pre and postsynaptic neurons are joined by gap junction. This
allows the local current resulted from arrived action potential to flow directly through the
connecting channels of gap junction and depolarizes the membrane of the postsynaptic.
Communication between neurons via electrical synapses is very fast. Numerous electrical
synapses are found in cardiac and smooth muscles, but rarely present in the mammalian nervous
system.
In chemical synapse as the axon of presynaptic neuron approaches postsynaptic neuron
branches and loses its myelin sheath. Each branch has a swelling at its terminus known synaptic
knob or synaptic button. The synaptic knob makes synapse with the soma or dendrite of
postsynaptic neuron. The membrane of synaptic knob is known as presynaptic membrane. A
o
small gap of 200 – 300 A exists between pre and post synaptic membrane which contains ECF
called as synaptic cleft. This small gap prevents direct propagation of the current from the
presynaptic neuron to the postsynaptic neuron. Signals are transmitted across the synaptic cleft
by means of a chemical messenger (a neurotransmitter) released from the presynaptic knob.
Occasionally more than one neurotransmitter may be simultaneously released from synaptic
knob and the additional neurotransmitters are called as cotransmitter. The synaptic knob
contains mitochondria and the synaptic vesicles filled with the neurotransmitter. The
postsynaptic membrane just opposite to synaptic knob has high density of membrane proteins
called the postsynaptic density. The neurotransmitters have different receptors on the
postsynaptic membrane. The release of neurotransmitter into the synaptic cleft is triggered with
the arrival of an action potential at the synaptic knob. The change in membrane potential due to
arrival of the action potential opens voltage-gated calcium channels in the presynaptic
membrane, and facilitates calcium influx into the axon terminal. The influxed calcium bind to a
synaptotagmin, a specific protein present on the wall of synaptic vesicle which mediates the
final fusion of the vesicle with the membrane of synaptic knob and subsequent exocytosis of
neurotransmitter.
After release from the presynaptic axon terminal, neurotransmitters diffuse across the
synaptic cleft. A part of these molecules bind to receptors on the postsynaptic density. The
binding of neurotransmitter to receptor causes the opening or closing of specific ligand gated ion
channels in the postsynaptic plasma membrane and leads to functional changes in that neuron. A
brief period of 0.2 second is required for passage of impulse from presynaptic neuron to
postsynaptic neuron because of the above sequence of events. This delay in passage of impulse at
synapse is called as synaptic delay. The ion channels in the postsynaptic membrane return to
their resting state when the neurotransmitter is no longer bound. Unbound neurotransmitters are
removed from the synaptic cleft by reuptake by presynaptic axon terminal or nearby glial cells,
diffuse away from the receptor site or enzymatically degraded.
Chemical synapses can be either excitatory or inhibitory as per the type of signal
transduction mechanism produced due to interaction of neurotransmitter and receptor at
postsynaptic membrane.

Excitatory Chemical Synapses

 At a synapse, if activated receptors open postsynaptic membrane ion channels permeable
to sodium, potassium, and other small, positively charged ions then these ions are move
according to the electrical and chemical gradients across the membrane. Opening channels to all
small positively charged ions, results in the simultaneous movement of a relatively small amount
of potassium ions out of the cell in comparison to large amount of sodium ions into the cell. This
movement of increased amount of positive ions into the postsynaptic neuron creates
depolarization. This potential change towards positive at post synaptic neuron is called an
excitatory postsynaptic potential (EPSP). The EPSP is a graded potential and spreads
decrementally away from the synapse by local current. Its only function is to bring the membrane
potential of the postsynaptic neuron closer to threshold.
Inhibitory Chemical Synapses
At inhibitory synapses, the potential change in the postsynaptic neuron is a
hyperpolarizing graded potential called an inhibitory postsynaptic potential (IPSP) due to
opening of either potassium channel or chloride channel without affecting sodium channels at
postsynaptic membrane. However, there is a short circuiting mechanism which causes inhibition
of neuron without development of IPSP. In some neurons the concentration of potassium ions
and chloride ions are such that the Nernst potential of these ions are equal to the resting
membrane potential of neuron. Therefore, even if potassium or chloride channels open, there is
no net transfer of ions across the membrane and no development of IPSP. However, if the neuron
is excited through other synapse causing inflow of sodium ions, the EPSP to be produced is
nullified or weakened due to opening of potassium or chloride channels. Hence, influx of sodium
ion is required to overcome potassium or chloride flux to produce EPSP.
Inhibition of a synapse may occur at presynaptic neuron even before the signal
reaches the synapse. This is known as presynaptic inhibition and mostly occurs in axo-axonic
synapse. This mechanism controls the release of neurotransmitters from axons. It is due to
binding of neurotransmitters to inhibitory receptors on the axon which suppresses the release of
neurotransmitters. There are different ways of presynaptic inhibition;
i. Axo-axonal transmission: A neurotransmitter released from axon of one neuron acts on
the receptors present on axon of another neuron to suppress the release of a
neurotransmitter from the axon of second neuron.
ii. Auto-inhibition: A neurotransmitter released from a neuron accumulates near the axon
terminal and activates presynaptic inhibitory receptors to suppress further release.
iii. Non-neural substances: Neurotransmitters released into synapses from non-neural
sources can act presynaptically to suppress neurotransmission.
iv. Modulation of calcium conductance: Intracellular second messengers modulate
presynaptic calcium conductance.
v. Axon terminal depolarization: The axon terminal persistently depolarized to inactivate
sodium channels and reduce magnitude of action potential induced voltage.
Properties of synapse:
i. One way conductance: Impulse transmission is always from presynaptic neuron to
postsynaptic neuron and never in reverse direction. This is also called as law of
dynamic polarity.
ii. Synaptic delay: Some time is required for the passage of impulses from presynaptic
neuron to postsynaptic neuron which is called as synaptic delay. Causes of synaptic
delay are time taken for release of neurotransmitter from presynaptic neuron, time
taken for diffusion of neurotransmitter through synaptic cleft, time taken for
neurotransmitter to bind with receptor on post synaptic membrane & to induce the
opening of ion channels, and time taken for diffusion of ions to change the resting
membrane potential of the postsynaptic membrane.
iii. Summation: Summation means stronger excitation of a postsynaptic neuron by
simultaneous stimulation of large number of presynaptic axon terminals (spatial
summation) or by a volley of stimuli in rapid succession through a single presynaptic
neuron (temporal summation).
iv. Convergence: When a number of presynaptic neurons secreting different excitatory and
inhibitory neurotransmitters form synapse with a single postsynaptic neuron, then
sum total of strength of these excitatory and inhibitory impulses will decide the type
of excitation produce by the postsynaptic neuron. The phenomenon is called
convergence.
v. Divergence: If a single presynaptic neuron forms synapse with a number of postsynaptic
neurons, then impulse from presynaptic neuron will be transmitted to each of the
postsynaptic neuron. The process is called divergence which helps in amplification of
 transmitted impulse.
vi. Occlusion: The combined effect of simultaneous stimulation of the two presynaptic
neurons is less than the sum of the effects produced when they were stimulated
individually. This process is called occlusion which occurs due to the sharing of
common post-synaptic neurons.
vii. Subliminal fringe: Response obtained by simultaneous stimulation of two presynaptic
neurons is greater than the sum total of the response obtained when they are
separately stimulated. Suppose two pre-synaptic neurons each excite five post-
synaptic neurons and subliminal fringe effect on two other post-synaptic neurons
which are common to both presynaptic neurons. Hence simultaneous stimulation of
both pre-synaptic neurons excite 12(5+5+2) post synaptic neurons as the subliminal
fringe effect on two neurons summated to produce threshold stimulation.
viii. Facilitation: When presynaptic neuron is stimulated with several consecutive
individual stimuli, each produces larger post synaptic potential than previous
stimulus. This is due to each succeeding stimulus causes more release of
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neurotransmitter due to prolonged opening of Ca channels.
ix. After discharge of synapse: After discharges are repetitive or sustained firing of action
potentials that occur after a single stimulation and persist beyond stimulus cessation.
x. Synaptic fatigue: Also known as short term synaptic depression. It is a temporary state
where neurons are unable to fire and transmit signals. It happens due to repeated
stimulation of excitatory synapses at a high rate. This leads to gradual reduction in
amount of discharge due to depletion of neurotransmitter.
xi. Reverberation: Passage of impulse from presynaptic neuron and again back to
presynaptic neuron to produce continuous stimulation of presynaptic neuron is known
as reverberation. This may be to formation of a synapse of axon or its collateral of a
presynaptic neuron with its own dendrite.
xii. Post-tetanic potentiation: A volley of high frequency stimulation for a brief period
followed by single stimulus produces a prolonged post-synaptic response. This form
of synaptic plasticity is due to calcium dependent activation of protein kinase that
increases the release of neurotransmitter containing vesicles.
Neurotransmitters and neuromodulators
Certain chemical messengers produce complex responses that cannot be described as EPSPs
or IPSPs, but can be described by the word “modulation”. The neuro-chemicals which produce
complex responses are called neuromodulators. It is very difficult to make distinctions between
neuromodulators and neurotransmitters. Certain neuromodulators are also synthesized by the
presynaptic neuron and co-released with the neurotransmitter. A number of hormones, paracrine
secretions act as neuromodulators. Neuromodulators may modify the response of postsynaptic
neuron to specific neurotransmitters. Synthesis, release, reuptake, or metabolism of neuro-
transmitter in presynaptic neuron may also be influenced by neuromodulators. Receptors for
neurotransmitters directly influence ion channels to produce excitation or inhibition in
postsynaptic neuron within a very short period of time (milliseconds). But the receptors for
neuromodulators influence metabolic processes in neurons which takes a longer period of time.
Acetylcholine (ACh):
ACh is a major neurotransmitter in the PNS at the neuromuscular junction and in the brain of
CNS. Nerve fibers that release ACh are called cholinergic fibers. Acetylcholine (ACh) is
synthesized from choline and acetyl coenzyme A in the cytoplasm of axon terminals and stored
in vesicles. After its release and activation of receptors on the postsynaptic membrane, the
concentration of ACh at synaptic cleft is reduced due to rapid destruction by the enzyme
acetylcholinesterase. This enzyme is present on the pre and postsynaptic membranes. The
choline, end product of enzymatic action is transported back into the presynaptic axon terminals
where it is reused in the synthesis of new ACh. The nerve gas Sarin, inhibits
acetylcholinesterase, causing accumulation of ACh in the synaptic cleft which results in
overstimulation of postsynaptic ACh receptors, rapidly making them fatigued and inducing
paralysis.
There are two types of ACh receptors according to their responsiveness to two different
drugs. Some ACh receptors respond to acetylcholine as well as to nicotine and, therefore, known
as nicotinic receptors. The nicotinic receptor itself contains a ligand-gated ion channel which is
selective for both sodium and potassium ions. Nicotinic receptors are present at the
neuromuscular junction. Some toxins are antagonistic to nicotinic receptor and induce paralysis.
Nicotinic receptors in the brain are important in cognitive functions like attention, learning, and
memory. Neurons associated with the ACh system degenerate in persons with Alzheimer’s
disease an age-related brain disease. The exact causes of the degeneration are unknown.
 The second type of cholinergic receptor is stimulated by acetylcholine and the mushroom
poison muscarine and these are called muscarinic receptors. These receptors are coupled with
G proteins and thus alter the activity of a number of different enzymes and ion channels. They
are mostly present at cholinergic synapses in the brain and at junctions of neurons that innervate
several glands and organs (heart).
Biogenic Amines
The biogenic amines are small charged molecules that are synthesized from amino acids
and contain an amino group (R–NH2). The most common biogenic amines are dopamine,
norepinephrine, serotonin, and histamine. Epinephrine is also a biogenic amine, but not a
common neurotransmitter in the CNS. It is a hormone secreted by the adrenal medulla.
Norepinephrine is an important neurotransmitter in both the CNS & PNS.
Catecholamines
Dopamine, norepinephrine (NE), and epinephrine all contain a catechol ring (a six-
carbon ring with two adjacent hydroxyl groups) and an amine group, hence are called as
catecholamines. The catecholamines are formed from the amino acid tyrosine at the axon
terminals. Synthesis and release of the catecholamines are strongly modulated by autoreceptors
on the presynaptic terminals. After activation of the receptors on the postsynaptic cell, the
catecholamine concentration in the synaptic cleft declines, mainly because the catecholamine is
actively transported back into the axon terminal by a membrane transporter protein. The
catecholamine neurotransmitters are also broken down in both the extracellular fluid and the
axon terminal by enzymes such as monoamine oxidase (MAO). These neurotransmitters play
essential roles in states of consciousness, mood, motivation, directed attention, movement,
blood-pressure regulation. Nerve fibers that release epinephrine or norepinephrine came to be
called adrenergic/ noradrenergic fibers.
There are two major classes of receptors for norepinephrine and epinephrine: alpha-
adrenergic receptors and beta-adrenergic receptors. All catecholamine receptors are
metabotropic (initiate metabolic processes). Beta-adrenoceptors (3 Sub classes) act via
stimulatory G proteins to increase cAMP in the postsynaptic cell. Alpha-adrenoceptors are of
two subclasses.
Serotonin
Serotonin (5-hydroxytryptamine or 5-HT) is an important biogenic amine, derived from
amino acid tryptophan. It works as a neuromodulator. Serotonin-releasing neurons innervate all
parts of the brain and spinal cord and produce its action through 16 types of receptor. The
activity of serotonergic neurons is lowest during sleep and highest during states of alert. These
fibers help in the regulation of food intake, reproductive behavior, and emotional states (ex.
mood and anxiety). Depression is treated by serotonin reuptake blockers (fluoxetine). These
drugs decrease appetite (side effect).
Amino Acid Neurotransmitters
Some amino acids themselves function as neurotransmitters and can be categorized in biogenic
amines. Those are mostly found in plenty in the CNS.
Glutamate and aspartate
Glutamate and aspartate are two excitatory neurotransmitters found in the CNS.
Glutamate has both metabotropic and ionotropic receptors. One ionotropic glutamate receptor is
the n-methyl-d-aspartate (NMDA) receptor associated with learning, memory, and neural
development. It is also involved in epilepsy and the neural damage and low oxygen availability.
GABA (gamma-aminobutyric acid) and glycine
These are the major inhibitory neurotransmitters in the CNS. GABA is not used to build
proteins, as it is a modified form of glutamate. GABA neurons are small interneurons that reduce
the activity within a neural circuit. GABA may bind to ionotropic or metabotropic receptors on
post synaptic membrane. The ionotropic receptors of GABA increase of influx chloride into the
cell, resulting in hyperpolarization of the postsynaptic neuron. The ionotropic receptor of GABA
has additional binding sites for other compounds (like steroids, barbiturates, and
benzodiazepines).
Neuropeptides
The neuropeptides contain two or more amino acids joined by peptide bonds. Many
neuropeptides discovered from non-neural tissues where they function as hormones or paracrine
agents. Neurons that release one or more of the peptide neurotransmitters are called peptidergic.
Neuropeptides may cosecreted along with neurotransmitter and act as neuromodulators. The
quantity of peptide neurotransmitter released at the synapse is less than the amount of
nonpeptidergic neurotransmitter. Neuropeptides can affect other neurons present away from its
site of secretion. Neuropeptides conjugate with either ionotropic or metabotropic receptors to
produce their action and afterwards broken down by peptidases present in the neuronl membrane.
Examples of neuropeptides are beta-endorphin, the dynorphins, and the enkephalins, substance
P.
Nontraditional neurotransmitters
Two gases nitric oxide and carbon monoxide act as neurotransmitters. Gases are not
released from presynaptic vesicles, nor do they bind to postsynaptic plasma membrane receptors.
They simply diffuse from their sites of origin in one cell into the intracellular fluid of nearby
cells. These gases serve as messengers between some neurons and between neurons and effector
cells. Both are produced by cytosolic enzymes and bind to and activate guanylyl cyclase in the
recipient cell. This increases the concentration of the second-messenger cyclic GMP in that cell.
Other nontraditional neurotransmitters are ATP and adenine (excitatory
neuromodulators). ATP is present in all presynaptic vesicles and is cosecreted with
neurotransmitter(s) in response to calcium influx into the terminal. Adenine is derived from ATP
via extracellular enzymatic activity. Adenine has both presynaptic and postsynaptic receptors.
The exact role played by these substances in neurotransmission is unknown.
Neuroeffector communication
Neuroeffector junctions are mainly formed by efferent neuron axon terminals or
varicosities on muscle and gland cells. The neurotransmitters released by these efferent neuron
axon terminals or varicosities provide the link through which electrical activity of the nervous
system can regulate effector cell activity. The events that occur at neuro effector junctions are
similar to those at a synapse. The neurotransmitter is released from the efferent neuron upon the
arrival of an action potential at the neuron’s axon terminals or varicosities. The neurotransmitter
then diffuses to the surface of the effector cell, where it binds to receptors on that cell’s plasma
membrane. The receptors on the effector cell may be associated with ion channels that alter the
membrane potential of the cell, or they may be coupled via a G protein to enzymes that result in
the formation of second messengers in the effector cell. The major neurotransmitters released at
neuroeffector junctions are acetylcholine and norepinephrine.
i.
When opposite electric charges come together they have the potentiality to do some
work. This potential is called an electrical potential which is determined by the difference in the
amount of charge between two points. Thus it is called potential difference or simply potential.
The electrical potential between charges makes them flow. This movement of electrical charge is
called a current. The current depends on the potential difference, the nature of the material or
structure through which they pass. The hindrance to electric current is known as resistance.
Materials that have a high electrical resistance reduce current flow and are known as insulators.
Materials that have a low resistance and allow rapid current flow are called conductors. Water
that contains dissolved ions is a relatively good conductor of electricity because the ions can
carry the current. As the intracellular and extracellular fluids contain many ions and can
therefore carry current. Lipids, contain very few charged groups, hence cannot carry current.
Therefore, the lipid layers of the plasma membrane are regions of high electrical resistance
separating the intracellular fluid and the extracellular fluid, with low resistance.
At resting conditions (undisturbed state) cells have a potential difference across cell
membranes. The inside of the cell is negatively charged with respect to the outside. This
potential across cell membrane is known as the resting membrane potential. The magnitude of
the resting membrane potential varies from about -5 to -100 mV, depending upon the type of cell.
Neurons exhibit resting membrane potential which varies between -40 to -90 mV. The resting
membrane potential does not change unless changes in potential across the membrane.
A sensory system is a part of the nervous system that consists of
1. sensory receptor cells (receive stimuli from the external or internal environment),
2. the neural pathways (conduct information from the receptors to the brain or spinal
cord), and
3. parts of the brain (processing the information).
Information processed by a sensory system may or may not lead to conscious awareness
of the stimulus. The information produces consciousness is called sensory information or
sensation. An individual’s understanding of the sensation’s meaning is called perception.
Sensations and perceptions occur after processing of sensory information by the CNS. This
processing can accentuate (make prominent), dampen (make less intense), or filter sensory
afferent information.
The initial step of sensory processing is the transformation of stimulus energy into graded
potential (the receptor potential) and then into action potentials in nerve fibers. The pattern of
action potentials in particular nerve fibers is a code that provides information about the
environment.
Sensory Receptors:
Information about the internal and external environment reaches the CNS via a variety of
sensory receptors. These receptors are transducers that convert various forms of energy in the
environment into action potentials in neurons. The term "receptor" is used in physiology to refer
not only to sensory receptors but also, to proteins that bind neurotransmitters, hormones, and
other substances with great affinity and specificity as initial step in initiating a specific
physiologic response.
 The sensory receptor may be part of a neuron or a specialized cell that generates action
potentials in neurons. The receptor is often associated with non-neural cells to form a sense
organ. The forms of energy converted by the receptors include mechanical, thermal,
electromagnetic, and chemical energy. The energy that acts upon and activates a sensory receptor
is known as a stimulus. The process by which a stimulus is transformed into an electrical
response is known as stimulus transduction. There are many types of sensory receptors, which
respond more specifically to one form of energy than to others. The type of energy to which a
particular receptor responds at a lower threshold than other receptors respond to this form of
energy is known as its adequate stimulus. Most sensory receptors are highly sensitive to
specific form of energy/ adequate stimulus. For example, some olfactory receptors respond to as
few as three or four odor molecules in the inspired air, and visual receptors can respond to a
single photon (the smallest quantity of light). However, all sensory receptors can be activated by
several forms of energy if the stimulus intensity is sufficiently high (higher than threshold level).
For example, the receptors of the eye normally respond to light, but they can be activated by an
intense mechanical stimulus, like a poke in the eye. A receptor gives rise to only one sensation
irrespective of its mode of stimulation.
Classifications of receptors:
I. Cutaneous Receptor: Receptors are present in the skin & concerned with perception of
external environment. Cutaneous senses are touch, pressure (sustained touch), cold,
warmth and pain.
Visceral Receptor: concerned with perception of internal environment.
II. Based on source of stimulus:
Teleceptors: Received stimulus from a distance
Exteroceptors: Concerned with external environment nearby.
Interoceptor: Concerned with internal environment.
Proprioceptor: Provide information about position of the body in space at any given
instant of time.
III. Based on type of stimulus:
Cutaneous receptors for touch and pressure are mechanoreceptors are
responsible for many types of sensory information, including touch, blood pressure,
and muscle tension. These stimuli alter the permeability of ion channels on the
receptive membrane, leading to change in the membrane potential.
Nociceptors are specialized nerve endings those respond to a number of different
painful stimuli, such as extreme heat and cold or tissue damage.
Chemoreceptors respond to the binding of particular chemicals to the receptive
membrane (stimulated by a change in chemical composition). This type of receptor is
used in the senses of smell and taste and in the detection of blood concentrations of
oxygen and carbon dioxide.
Thermoreceptors detect both sensations of coldness and warmth.
Photoreceptors respond to particular light wavelengths.
IV. Based on adaptation:
Slowly adapting/ Tonic/ Static Receptor: Continuously fire AP
Rapidly adapting/ Phasic/ Dynamic Receptor: Fire AP in a decreasing order.
The transduction process in sensory receptors involves the opening or closing of ion
channels. The ion channels are present in a specialized receptor membrane located at the distal
tip of the neuronal process or on the receptive membrane of specialized sensory cells. The gating
of these ion channels allows a change in the ion fluxes across the receptor membrane, which in
turn produces a change in the membrane potential. This change in potential is a graded potential
and called as receptor potential. The changes in ion channels of specialized receptor membrane
do not generate action potentials. Instead, local current from the receptor membrane flows a short
distance along the axon to a region where the membrane has voltage-gated ion channels and can
generate action potentials. In myelinated afferent neuron, this region is present at the first node of
Ranvier of the myelin sheath. The receptor potential, like the synaptic potential is a graded
response to different stimulus intensities and slows down as it is propagated across the
membrane. If the receptor membrane is on a separate cell, the receptor potential there alters the
release of neurotransmitter from that cell. The neurotransmitter diffuses across the extracellular
cleft between the receptor cell and the afferent neuron and binds to specific sites on the afferent
neuron. The combination of neurotransmitter with its binding sites on the afferent neuron
generates a graded potential in the neuron’s dendrite. The magnitude of receptor potential
decreases with distance from its origin. However, if the amount of depolarization at the first node
of Ranvier in the afferent neuron is large enough to bring the membrane to threshold, action
potentials are initiated, which then propagate along the nerve fiber. The only function of the
graded potential is to trigger action potentials. As long as the afferent neuron remains
depolarized to or above threshold, action potentials continue to fire and propagate along the
afferent neuron. Moreover, because the magnitude of a graded potential determines the distance
it will travel and its duration, an increase in the graded potential magnitude causes an increase in
the action potential frequency in the afferent neuron. Although the graded potential magnitude
determines action potential frequency, it does not determine action potential magnitude. Since
the action potential is all-or-none, its magnitude is independent of the strength of the initiating
stimulus. Factors that control the magnitude of the receptor potential include stimulus strength,
rate of change of stimulus strength, temporal summation of successive receptor potentials and
adaptation. This last process is a decrease in receptor sensitivity, which results in a decrease in
the frequency of action potentials in an afferent neuron despite maintenance of the stimulus at
constant strength. The degrees of adaptation vary widely between different types of sensory
receptors.
Primary Sensory Coding
Conversion of receptor potentials into a pattern of action potentials that conveys sensory
information to the CNS is called coding. Characteristics of the stimulus such as type, intensity,
duration, and location are encoded within the excitable cells. This coding begins at the receptive
neurons in the peripheral nervous system. A single afferent neuron with all its receptor endings
makes up a sensory unit. In a few cases, the afferent neuron has a single receptor. Normally the
peripheral end of an afferent neuron divides into many fine branches, each terminating with a
receptor. The portion of the body when stimulated produces activity in a particular afferent
neuron, is called the receptive field for that neuron. Receptive fields of neighboring afferent
neurons overlap so that stimulation of a single point activates several sensory units. So activation
at a single sensory unit almost never occurs.
Another term for stimulus type is stimulus modality. Modalities can be divided into
submodalities: Cold and warm are submodalities of temperature, whereas salt, sweet, bitter, and
sour are submodalities of taste. The type of sensory receptor activated by a stimulus plays the
primary role in coding the stimulus modality. A given receptor type is sensitive to an adequate
stimulus, because of the signal transduction mechanisms and ion channels incorporated in the
receptor’s plasma membrane. Ex. receptors for vision contain pigment molecules whose shape is
transformed by light. This modification in pigment molecules alter the activity of ion channels in
membrane and generate a neural signal. In contrast, receptors in the skin have neither light-
sensitive molecules nor plasma membrane ion channels that can be affected by them; thus,
receptors in the eyes respond to light and those in the skin do not. All the receptors of a single
afferent neuron are preferentially sensitive to the same type of stimulus. For example, they are all
sensitive to cold or all to pressure. Adjacent sensory units may be sensitive to different types of
stimuli. As the receptive fields for different modalities overlap, a single stimulus can give rise
simultaneously to the different sensations (an ice cube on the skin can produce the sensation of
touch and temperature).
The increased stimulus strength produces a larger receptor potential and firing of frequent
action potential. In addition to an increased firing rate from individual receptors, receptors on
other branches of the same afferent neuron also begin to respond. The action potentials generated
by these receptors propagate along the branches to the main afferent nerve fiber and add to the
series of action potentials there. In addition to increasing the firing frequency in a single afferent
neuron, stronger stimuli usually affect a larger area and activate similar receptors on the endings
of other afferent neurons. For example, when one touches a surface lightly with a finger, the area
of skin in contact with the surface is small, and only receptors in that skin area are stimulated.
Pressing down firmly increases the area of skin for stimulation. The stimulation of receptors on
additional afferent neurons is known as recruitment.
A third type of information to be signaled is the location of the stimulus i.e., where the
stimulus is being applied. In vision, hearing, and smell, stimulus location is interpreted as arising
from the site from which the stimulus originated rather than the place on our body where the
stimulus was actually applied. For example, we interpret the sight and sound of a barking dog as
occurring on the other side of the fence rather than in a specific region of our eyes and ears. The
main factor that codes for stimulus location is the site of the stimulated receptor. The precision,
or acuity, with which one stimulus can be located and differentiated from an adjacent one,
depends upon the amount of convergence of neuronal input in the specific ascending pathways.
Greater the convergence lesser the acuity. Other factors affecting acuity are the size of the
receptive field covered by a single sensory unit and the amount of overlap of nearby receptive
fields. For example, it is easy to discriminate between two adjacent stimuli applied to the skin on
your lips, where the sensory units are small and the overlap considerable. It is harder to do so on
the back, where the sensory units are large and widely spaced. Locating sensations from internal
organs is less precise than from the skin because there are fewer afferent neurons in the internal
organs and each has a larger receptive field. An afferent neuron responds most vigorously to
stimuli applied at the center of its receptive field because the receptor density. The response
decreases as the stimulus is moved toward the receptive field periphery. Thus, a stimulus
activates more receptors and generates more action potentials if it occurs at the center of the
receptive field. The firing frequency of the afferent neuron is also related to stimulus strength.

Pacinian Corpuscles

The pacinian corpuscles are touch receptors. Each capsule consists of the straight, unmyelinated
ending of a sensory nerve fiber (2 µm in diameter) surrounded by concentric lamellas of
connective tissue that give the organ the appearance of a onion. The myelin sheath of the sensory
nerve begins inside the corpuscle. The first node of Ranvier is also located inside, whereas the
second is usually near the point at which the nerve fiber leaves the corpuscle

Adaptation

When a sense organ/ receptor is continuously stimulated the frequency of the action potentials in
its sensory nerve declines over time. This phenomenon is known as adaptation or
desensitization. The degree to which adaptation occurs varies from one sense organ to another.
Doctrine of Specific Nerve Energies

The specific sensation created by impulses generated in a receptor depends upon the specific part
of the brain they ultimately activate. The specific sensory pathways are discrete from sense organ
to specific part of brain. Therefore, when the nerve pathways from a particular sense organ are
stimulated, the sensation produced specific for the receptor. This principle is called doctrine of
specific nerve energies first proposed by Muller in 1835. For example, if the sensory nerve from
a pacinian corpuscle in the hand is stimulated by pressure at the elbow or by irritation from a
tumor in the brachial plexus, the sensation evoked is touch. Similarly, if a fine electrode inserted
into the fibers of the dorsal columns of the spinal cord, the thalamus, or the postcentral gyrus of
the cerebral cortex, the sensation produced by stimulation will be touch. This doctrine is in
question for the nociceptor pathway that signals both heat and pain.
Projection

No matter where a particular sensory pathway is stimulated along its course to the cortex, the
conscious sensation produced is referred to the location of the receptor. This principle is called
the law of projection. For example, when the cortical receiving area for impulses from the left
hand is stimulated, the patient reports sensation in the left hand, not in the head. Another
dramatic example is seen in amputees. Some of these patients may complain of pain and
proprioceptive sensations in the absent limb (phantom limb). The ends of the nerves cut at the
time of amputation often form nerve tangles called neuromas. These may discharge
spontaneously or when pressure is put on them. The impulses that are generated are in nerve
fibers that previously came from sense organs in the amputated limb, and the sensations evoked
are projected to where the receptors used to be.
Intensity Discrimination
There are two ways in which information about intensity of stimuli is transmitted to the brain; by
variation in the frequency of the action potentials generated by the activity in a given receptor,
and by variation in the number of receptors activated. It has long been taught that the magnitude
of the sensation felt is proportionate to the log of the intensity of the stimulus (Weber-Fechner
law).

Sensory Units

The term "sensory unit" is applied to a single sensory axon and all its peripheral branches. The
receptive field of a sensory unit is the area from which a stimulus produces a response in that
unit.

Recruitment of Sensory Units

As the strength of a stimulus is increased, it tends to spread over a large area and generally not
only activates the sense organs immediately in contact with it but also "recruits" those in the
surrounding area.
Classification of Nerve Fibers
Nerve fibers are mainly classified in two different ways; general classification which
include both sensory and motor fibers as well as autonomic nerve fibers and in other
classification only sensory fibers are classified.
In general classification, the fibers are divided into type A & type C fibers. The type A
fibers are again subdivided into α, β, γ, and δ fibers. Type A fibers are myelinated spinal nerves,
whereas C fibers are small and unmyelinated fibers.
Aα Fiber: Diameter: 13-20 µm, myelinated, Conduction velocity: 80 – 120 m/s, associated with
extrafusal muscle fibers.
Aβ Fibers: Diameter: 6 - 12 µm, myelinated, Conduction velocity: 33 – 75 m/s, associated with
mechanoreceptors.
Aγ Fibers: Diameter: 5 - 8 µm, myelinated, Conduction velocity: 4 - 24 m/s, associated with
intrafusal muscle fibers.
Aδ Fibers: Diameter: 1 - 5 µm, myelinated, Conduction velocity: 3 - 30 m/s, associated with noci
ceptors, free nerve endings.
C Fibers: Diameter: 0.2 – 1.5 µm, non-myelinated, Conduction velocity: 0.5 – 2.0 m/s,
associated with nociceptors, and warmth receptor.
It is too difficult to differentiate between Aβ and Aγ fibers
Alternate classification:
Group Ia fibers: Equivalent to Aα Fiber. Diameter: 13-20 µm, myelinated, Conduction velocity:
80 – 120 m/s, associated with muscle spindle.
Group Ib fibers: Equivalent to Aα Fiber. Diameter: 13-20 µm, myelinated, Conduction velocity:
80 – 120 m/s, associated with extrafusal muscle fibe, Golgi tendon organ.
Group II Fibers: Equivalent to Aβ Fiber. Diameter: 6-12 µm, myelinated, Conduction velocity:
33 – 75 m/s, associated with mechanoreceptors.
Group III Fibers: Equivalent to Aδ Fiber. Diameter: 1-5 µm, myelinated, Conduction velocity: 3
- 30 m/s, associated with nociceptors, & free nerve endings.
Group IV Fibers: Equivalent to C Fiber Diameter: 0.2 – 1.5 µm, non-myelinated, Conduction
velocity: 0.5 – 2.0 m/s, associated with nociceptors, and warmth receptor.
REFLEXES
Reflex Arc:
The basic unit of integrated neural activity is a reflex arc. A reflex arc consists of a
sensory organ, an afferent neuron, one or more interneurons in the spinal cord, an efferent
neuron, and an effector organ. The cell body of afferent neuron is present at the dorsal root
ganglia. The interneurons integrate the information sent by the sense organ and in this process of
integration, the brain may be involved. The efferent neuron originates from the ventral horn and
goes to the site of action (the effector). While the afferent neuron is sensory, the efferent neuron
is motor.
The number of synapses formed in CNS in the course of the reflex arc may be one or
more. The reflex arc in which only one synapse is involved is known as monosynaptic reflex.
Example of monosynaptic reflex is "Stretch Reflex". In polysynaptic reflex arc one or more
interneurons are involved, hence more than one synapse are present.
Monosynaptic Reflex:
The stretch reflex of the skeletal muscle is the only monosynaptic reflex in the body. Two
sensory organs are involved in the stretch reflex: 1. Muscle Spindle and 2. Golgi Tendon Organ.
Muscle Spindle:
Muscle spindle is formed by three to ten muscle fibers encapsulated in a connective tissue
capsule. These encapsulated muscle fibers are called as "Intrafusal Fibers". Other fibers outside
capsule in muscle are known as "Extrafusal Fibers". The intrafusal fibers are present in normally
in the perimysial spaces and their capsules are connected to the sheath of the extrafusal fibers.
The intrafusal fibers are normally smaller than extrafusal fibers.
In a muscle spindle two types of intrafusal fibers are present; 1. Nuclear Bag Fibers and
2. Nuclear Chain Fibers.
Nuclear Bag Fibers:
Nuclear Bag Fibers do not have actin and myosin in their central portion and hence,
central portion is not able to contract. But the two peripheral portions do contain the contractile
proteins and hence able to contract. The central portion of these fibers contains a number of
nuclei, hence such fibers are known as "Nuclear Bag Fibers".
Nerve endings remain surrounding the central portion of nuclear bag fibers. These nerve
endings are sensory in nature and called as 'Primary' or 'Annulospiral' nerve endings. These
sensory nerve endings give rise to Ia (myelinated & largest diametered) nerve fibers. The Ia
fibers pass through the dorsal horn of spinal cord straight to the ventral horn where those end on
alpha motor neurons. Alpha motor neurons supply the skeletal muscles of which muscle spindle
is a part.
The two contractile ends of nuclear bag fibers are supplied with gamma efferent neuron.
30% of the motor nerves originating from ventral horn are gamma motor fibers.
Nuclear Chain Fibers:
Nuclear Chain Fibers are smaller than the nuclear bag fibers. These fibers central portion
also contains annulospiral nerve endings which give rise to Ia fibers. But in addition to the
primary nerve endings, there are also secondary nerve endings around the nuclear chain fibers
which give rise to group-II fibers. These group-II fibers go to CNS and end on interneurons on
which collaterals of group-Ia fibers also end. These interneurons send signals to the ventral horn
for a longer period.
Dynamic Action of Muscle Spindle:
When the muscle gets stretched intrafusal fibers are also stretched. So, the annulospiral
nerve endings also get stretched. If the length of extrafusal fibers is increased, then the
annulospiral nerve endings are strongly stimulated. Hence, the muscle contracts due to the strong
impulse from the alpha motor neuron. This is called dynamic action of the muscle spindle.
Static Action of Muscle Spindle:
If the extrafusal fibers are no more increasing, but have increased more than usual, then
the endings of secondary (group-II) fibers send impulses to CNS for a long period (even more
than a hour). This phenomenon is called Static function of muscle spindle.
Role of Gamma Motor Neuron:
Gamma Motor Neurons are a group of lower motor neuron present in the ventral horn of
the spinal cord. Cell bodies of these neurons are present in anterior grey column of the spinal
cord. These are also known as 'Fusimotor Neurons'. They don't directly adjust the lengthening or
shortening of muscles. When impulses are arriving at the two ends of the intrafusal fibers
through gamma motor neurons, both the ends of the intrafusal fibers get stretched. This causes
stimulation of annulospiral nerve endings which in turn stimulates the alpha motor neuron and
results in muscle contraction. The skeletal muscle is always in partial contraction and this is due
to the activity of the gamma motor neuron. This partial contraction of muscles is called ‘muscle
tone’ which is maintained by feedback/ servo mechanism of gamma motor neuron.

Golgi Tendon Organ:

The muscle spindle gets excited due to the stretching of the muscle spindle, but the Golgi
tendon organ is excited due to strong stretching or contraction of the muscle which makes the
tendon strongly stretched. The Golgi tendon organ consists of knobby nerve endings interspersed
in the fascicles of the tendon involving 3 - 25 muscle fibers. The receptor endings give rise to Ib
nerve fibers which pass to spinal cord through dorsal horn and ends on inhibitory interneurons.
These interneurons end on end on alpha motor neuron. They also make excitatory connections
with motor neurons supplying antagonistic muscles.
When muscle is strongly contracting or passively stretched strongly at that time Golgi
tendon organ gets stimulated. This stimulus passes to spinal cord through Ib afferent fibers. It
inhibits alpha motor neuron supplying muscle whose tendon is strongly stretched. Then this
muscle suddenly relaxed as it is inhibited by the interneurons protecting the muscle from rupture.
This reflex is called 'Inverse Stretch Reflex'.
Polysynaptic Reflex:
In case of poly synaptic reflexes, the afferent nerve after entering into the spinal cord gets
divided into a number of branches. Each of these branch end on different synaptic pathway and
lastly end on motor neuron. The synaptic pathway having least number of synapses sends the
impulse first to motor neuron and the synaptic pathway having largest number of synapses is the
last to send the impulse to motor neuron. Hence there is a prolonged bombardment of impulses
to the motor neuron that produces a prolonged response. Some of the branches turn on
themselves and form reverberating pathways which reverberate the activity till the activity dies
out. So, these reverberating pathways continue to stimulate the motor neuron for a prolonged
period.
Withdrawal reflex is a polysynaptic reflex. When there is a painful stimulation on the
skin of the leg of an animal, the animal withdraws the leg from the source of pain stimulus. In
such case, while flexor muscle is stimulated, the extensor muscle is inhibited. So, the limb is
withdrawn. Simultaneously the extensor muscle of the other limb is stimulated. These actions are
mediated through a number of synapses and reverberating pathways are present in brain and
spinal cord.