1 Definition

2 Classification of Synapse

Synapse is classified by two methods:

Anatomical Classification

Synapse is formed by axon of one neuron ending on cell body, dendrite or axon of the next neuron.

First neuron from which the axon arises is called presynaptic neuron.

Second neuron on which the axon of first neuron ends is called postsynaptic neuron.

Depending upon ending of axon, synapse is classified into three types:

Functional Classification

Depending upon function, synapse is classified into two types:

3 Functional Anatomy of Chemical Synapse

Axon of presynaptic neuron divides into many small branches before forming the synapse.

These branches are known as presynaptic axon terminals.

Membrane of presynaptic axon terminal is called presynaptic membrane.

Presynaptic axon terminal has two important structures:

1. Mitochondria, which help in the synthesis of neurotransmitter substances.
2. Synaptic vesicles, which store neurotransmitter substance.

Membrane of the postsynaptic neuron is called postsynaptic membrane.

It contains some receptor proteins.

A small space in between presynaptic membrane and postsynaptic membrane is called synaptic cleft.

Basal lamina of this cleft contains cholinesterase, which destroys acetylcholine.

4 Functions of Synapse

Function of the synapse is to transmit impulses from one neuron to another.

However, some synapses inhibit the impulses.

Accordingly, synapse is divided into two types:

Excitatory Synapse

Excitatory synapse transmits the impulses from presynaptic neuron to postsynaptic neuron by development of excitatory postsynaptic potential.

Excitatory Postsynaptic Potential: EPSP

Sequence of Synaptic Transmission

1. Arrival of action potential at axon terminal.
2. Opening of calcium channels in presynaptic membrane.
3. Influx of calcium ions from ECF into axon terminal.
4. Opening of vesicles and release of acetylcholine.
5. Passage of acetylcholine through synaptic cleft.
6. Formation of acetylcholine-receptor complex.
7. Opening of sodium channels and influx of sodium ions from ECF.
8. Development of EPSP.
9. Opening of sodium channels in initial segment of axon.
10. Influx of sodium ions from ECF and development of action potential.
11. Spread of action potential through postsynaptic neuron.

Mechanism of Excitatory Synaptic Transmission

When action potential reaches the presynaptic axon terminal, voltage-gated calcium channels are opened.

Calcium ions enter the axon terminal from ECF.

Calcium induces bursting of synaptic vesicles and release of neurotransmitter.

Now, the neurotransmitter diffuses through the synaptic cleft and enters the synaptic membrane by means of exocytosis.

Common neurotransmitter is acetylcholine.

Neurotransmitter binds with receptor protein present in postsynaptic membrane to form neurotransmitter-receptor complex.

Neurotransmitter-receptor complex causes opening of ligand-gated sodium channels.

Sodium ions enter the cell body of postsynaptic neuron from ECF.

Since sodium ions are positively charged, the resting membrane potential inside the cell body becomes slightly positive and mild depolarization develops.

This mild depolarization is called excitatory postsynaptic potential (EPSP).

Properties of EPSP

1. EPSP is nonpropagated.
2. It does not obey all-or-none law.

Significance of EPSP

EPSP is not transmitted into the axon of postsynaptic neuron.

However, it causes development of action potential in the axon.

When EPSP is strong enough, it causes opening of voltage-gated sodium channels in the initial segment of axon.

Due to entrance of sodium ions, depolarization occurs in the initial segment of axon and thus action potential develops.

From here, action potential spreads to other segments of the axon.

5 Synaptic Inhibition

Inhibition of synaptic transmission is classified into three types:

1. Postsynaptic inhibition
2. Presynaptic inhibition
3. Renshaw cell inhibition

1. Postsynaptic Inhibition

Postsynaptic inhibition or direct inhibition is a type of synaptic inhibition due to the release of an inhibitory neurotransmitter from presynaptic terminal instead of an excitatory neurotransmitter substance.

Inhibitory neurotransmitter develops inhibitory postsynaptic potential (IPSP) instead of EPSP.

Inhibitory neurotransmitters are gamma-aminobutyric acid (GABA), dopamine and glycine.

Development of IPSP: Action of GABA

IPSP is an electrical potential in the form of hyperpolarization that develops in the postsynaptic membrane by binding with receptor.

The inhibitory neurotransmitter GABA acts on postsynaptic membrane by binding with receptor.

Neurotransmitter-receptor complex opens the ligand-gated potassium channels instead of sodium channels.

Potassium ions which are available in plenty in the cell body of postsynaptic neuron move to ECF.

Simultaneously, chloride channels also open and chloride ions move from ECF into the cell body of postsynaptic neuron.

Exit of potassium ions and influx of chloride ions make the negativity inside the cell more, leading to hyperpolarization.

Hyperpolarized state of the synapse inhibits synaptic transmission.

2. Presynaptic Inhibition

Presynaptic or indirect inhibition is a type of synaptic inhibition that occurs due to failure of presynaptic axon terminal to release adequate quantity of excitatory neurotransmitter substance.

Presynaptic inhibition is mediated by axoaxonic synapses.

It is prominent in spinal cord and regulates the propagation of information to higher centers in brain.

Normally, during synaptic transmission, action potential reaching the presynaptic neuron produces development of EPSP in the postsynaptic neuron.

But, in spinal cord, a modulatory neuron called presynaptic inhibitory neuron forms an axoaxonic synapse with the presynaptic neuron.

This inhibitory neuron inhibits presynaptic neuron and decreases the magnitude of action potential in presynaptic neuron.

This smaller action potential reduces calcium influx.

This in turn decreases the quantity of neurotransmitter released by presynaptic neuron.

So, the magnitude of EPSP in postsynaptic neuron is decreased resulting in synaptic inhibition.

3. Renshaw Cell Inhibition

This is a type of synaptic inhibition caused by Renshaw cells in spinal cord.

Renshaw cells are small motor neurons scattered among the large α-motor neurons in anterior gray horn of spinal cord.

Motor nerve fibers that project to effector organs arise from α-motor neurons.

Some of these fibers send collateral fibers to Renshaw cells.

When motor neurons send motor impulses to effector organs, some of the impulses reach Renshaw cell by passing through collaterals.

Now, Renshaw cell is stimulated.

This, in turn, sends inhibitory impulses to α-motor neurons, so that discharge from α-motor neurons is reduced.

Significance of Synaptic Inhibition

6 Properties of Synapse

1. One-Way Conduction: Bell-Magendie Law

According to Bell-Magendie law, the impulses are transmitted only in one direction, i.e. from presynaptic neuron to postsynaptic neuron.

2. Synaptic Delay

Synaptic delay is a short delay that occurs during transmission of impulses through the synapse.

It is due to the time taken for:

1. Release of neurotransmitter.
2. Passage of neurotransmitter from axon terminal to postsynaptic membrane.
3. Action of neurotransmitter to open the ionic channels in postsynaptic membrane.

Synaptic delay is one of the causes for reaction time of reflex activity.

Significance of Determining Synaptic Delay

Determination of synaptic delay helps to find out whether the pathway for a reflex is monosynaptic or polysynaptic.

3. Fatigue

During continuous muscular activity, synapse forms the site of fatigue along with Betz cells present in the area of frontal lobe of cerebral cortex.

Fatigue at the synapse is due to depletion of acetylcholine neurotransmitter.

Depletion of acetylcholine occurs by two factors:

1. Soon after the action, acetylcholine is destroyed by diacetylcholinesterase.
2. Due to continuous action, new acetylcholine is not synthesized.

Above factors lead to depletion of acetylcholine resulting in fatigue.

4. Summation

Increased EPSP triggers the formation of action potential in initial segment of the postsynaptic neuron.

Spatial Summation

Spatial summation occurs when many presynaptic terminals are stimulated simultaneously.

Temporal Summation

Temporal summation occurs when one presynaptic terminal is stimulated repeatedly.

5. Electrical Property

Electrical properties of the synapse are the EPSP and IPSP.

Convergence and Divergence

Convergence is the process by which many presynaptic neurons terminate on a single postsynaptic neuron.

Divergence is the process by which one presynaptic neuron terminates on many postsynaptic neurons.

7 Neurotransmitters

Definition

Classification of Neurotransmitters

Neurotransmitters are classified by two methods:

1. Depending upon chemical nature
2. Depending upon function

Classification Depending Upon Chemical Nature

1. Amino acids
2. Amines
3. Others

Classification Depending Upon Function

1. Excitatory neurotransmitters which are responsible for the conduction of impulse.
2. Inhibitory neurotransmitters which inhibit the conduction of impulse.

Transport and Release of Neurotransmitter

Neurotransmitter is produced in the cell body of neuron and is transported through axon.

At axon terminal, the neurotransmitter is stored in small vesicles called vesicles.

Under the influence of a stimulus, vesicles get ruptured and release the neurotransmitter into synaptic cleft.

Neurotransmitter now binds to specific receptors on the surface of postsynaptic cell.

Neurotransmitters According to Chemical Nature

Excitatory and Inhibitory Neurotransmitters

GABA = Gamma-aminobutyric acid, CNS = central nervous system, GI = Gastrointestinal.

8 Neuromodulators

Neuromodulators vs Neurotransmitters

Neuromodulators are distinct from neurotransmitters.

However, both the terms are wrongly interchanged.

Neurotransmitters propagate nerve impulses through synapses, whereas neuromodulators modify and regulate the activities of synaptic transmission.

Neurotransmitters are packed in small vesicles in nerve terminals only.

But neuromodulators are generally packed in large synaptic vesicles, which are present in all parts of neuron like soma, dendrite, axon and nerve endings.

Many neurons have one conventional neurotransmitter and one or more neuromodulators.

Few peptides act as neurotransmitters and neuromodulators.

Differences Between Neurotransmitters and Neuromodulators

Actions of Neuromodulators

1. Regulation of synthesis, breakdown or reuptake of neurotransmitter.
2. Excitation or inhibition of membrane receptors by acting independently or together with neurotransmitter.
3. Control of gene expression.
4. Regulation of local blood flow.
5. Promotion of formation of new synapses.
6. Control of glial cell morphology.

Chemistry of Neuromodulators

Generally, neuromodulators are peptides.

So, neuromodulators are often called neuropeptides.

Almost all the peptides found in nervous tissues are neuromodulators.

Types of Neuromodulators

Neuromodulators are classified into two types:

1. Opioid neuromodulators which act by binding with opioid receptors located in nerve endings in brain and GI tract.
2. Nonopioid neuromodulators which act by binding with G-protein-coupled receptors.

Opioid Neuromodulators

Nonopioid Neuromodulators

ANP = Atrial natriuretic peptide, BNP = Brain natriuretic peptide, CCK = Cholecystokinin, CNP = C-type natriuretic peptide, CRH = Corticotropin-releasing hormone, GHRH = Growth hormone-releasing hormone, GHRP = Growth hormone-releasing polypeptide, GnRH = Gonadotropin-releasing hormone, TRH = Thyrotropin-releasing hormone, VIP = Vasoactive intestinal polypeptide.