Synaptic Cleft

As the name suggests, synaptic cleft, like other clefts, must be an empty space between two things. But it has some connections with brain and neurology.

A synaptic cleft is a space that separates two neurons. It forms a junction between two or more neurons and helps nerve impulse pass from one neuron to the other.

In this article, we will talk about different aspects
of synaptic cleft, its anatomy, and functions. You will completely understand
the concept of synapse after reading this article. So, stay tuned.

Anatomy of Synaptic Cleft

A synaptic cleft is not only a space between two neurons. It acts as a junction, connecting two or more neurons with one another.

Synaptic cleft is present between two neurons; a
pre-synaptic or pre-junctional neuron, and a post-synaptic or post-junctional
neuron.

Depending on the type of nerve fiber participating in the formation of synapse, there are following types of synaptic clefts:

Axo-axonic synapse

In this case, the synaptic cleft is present between two axons. The axon of one neuron makes synapse with axon of the other neuron.

Axo-dendritic synapse

In this case, the synaptic cleft is present between
axon and dendrite. The axon of one neuron makes synapse with dendrites of other
neurons.

Axo-somatic synapse

In this case, the synaptic cleft is present between axon and cell body or soma. The axon of one neuron makes synapse with the cell body of the other neurons.

On one end, a synaptic cleft has an axon and on the
other end, it is bounded by either a dendrite, cell body or axon of the other
neuron.

How synaptic cleft aids in nerve impulse transmission?

Synaptic cleft is essential for the transmission of
nerve impulses from one neuron to the other, in case of a chemical synapse.

A chemical synapse is a type of synapse in which nervous signal is transmitted from one neuron to the other through the chemicals that are released in the synaptic cleft. These chemicals are called neurotransmitters.

When a nerve impulse reaches the axon terminal of a pre-synaptic neuron, it causes degranulation of the vacuoles containing neurotransmitters.

Synaptic cleft provides a space to these neurotransmitters to diffuse and act on post-synaptic or post-junctional neurons. Neurotransmitters can also pile up in the synaptic cleft.

The size of a synaptic cleft is usually of the order of 20nm or 0.02 micrometer. This small size of the cleft allows the neurotransmitters to soon pile up in this tiny space.

The concentration of neurotransmitters immediately rises. They can act on the post-synaptic neurons and perform their action.

The small size of synaptic cleft also allows the
neurotransmitter concentration to be lowered rapidly. This is done by different
enzymes present in synaptic cleft. We will discuss these enzymes in the subsequent
heading.

Functions

Synaptic cleft performs the following functions in a chemical synapse.

Fusion of Neurotransmitters

Neurotransmitters are released by the pre-synaptic neurons. Synaptic cleft provides the space to these neurotransmitters to diffuse through and act on the post-synaptic neurons.

It allows the neurotransmitters to pile up and diffuse to act on the post-junctional neurons.

Degradation of Neurotransmitters

Synaptic cleft also harbors different enzymes. These enzymes are involved in the degradation of the released neurotransmitters. They can rapidly degrade the neurotransmitters and decrease their concentration.

This depletion of neurotransmitters impedes the nerve impulse transmission.

Regulation of Nerve Impulse Transmission

Synaptic cleft also plays a role in the regulation of nerve impulse transmission. The neurotransmitters released into the synaptic cleft are much greater than that required to excite the next neuron.

As mentioned earlier, synaptic cleft harbors enzymes that can degrade neurotransmitters. This degradation of neurotransmitters regulates the nerve impulse transmission.

Rapid degradation of excessive neurotransmitters prevents excessive excitation of the post-junctional neurons. As a result, the post-junctional neuron is excited to a limited level, preventing its excess excitation.

Site of Drug Action

Synaptic cleft also acts as a site of action of
various drugs. Most of these drugs are the agonists or antagonists of neurotransmitters.
They are used in a number of neurologic conditions. These drugs are discussed
below in another heading.

Diseases associated with Synaptic Alterations

It is now considered that in addition to other factors, alterations in the structure of synapse or synaptic cleft may play an important role in some neurologic and psychiatric conditions. Below is a brief review of some of these diseases.

Autism Spectrum Disorder

This disease has a spectrum of disorders including autism, Asperger syndrome and pervasive developmental disorder. The patients have the common symptoms of lack of social communication, delay of language and stereotypy.

It is now considered that alterations at the synaptic level play an important role in pathogenesis of this disease. Mutations affecting the adhesion molecules in the synaptic cells have been seen to be associated with Autism Spectrum Disorder.

Fragile X Syndrome: Mental Retardation

Fragile X syndrome is the most common inherited form
of mental retardation. The disease is characterized by reduced intellectual
ability, anxiety, hyperactivity, developmental delay and hypersensitivity to
stimuli. Many studies mental retardation in FXR is associated with alterations
in synapse development and function.

Alzheimer’s Disease

It is a neurodegenerative disorder affecting people in their older age. A significant association has been found between synapse alteration and Alzheimer’s disease.

A-beta amyloid formed in Alzheimer’s disease can cause a significant decrease in synaptic plasticity. In addition, Alzheimer’s disease is also characterized by decreased number of synapses in hippocampus, cerebral cortex and subcortical regions of the brain.

Addiction

Synaptic alteration has also been seen with different
types of addictions. Chronic administration of drugs results in changes in
dendritic spines and synaptic proteins. It also affects synaptic plasticity.
Preventing drug-induced modifications in synapse changes can provide treatment
for drug addiction.

Drugs that act in Synaptic Cleft

As said earlier, synaptic cleft acts as a site of
action of different drugs. These drugs include the following.

Curare drug

It is a drug that stops the action of acetylcholine at postsynaptic neuron. It is a non-depolarizing muscle relaxant that blocks the activation of acetylcholine receptors. It acts through the synaptic cleft and prevents the depolarization of post-synaptic neuron.

Strychnine

It is a poisonous drug acting mainly on motor neurons
in the spinal cord. It acts through the synaptic cleft and blocks the
activation of acetylcholine and glycine receptors causing uncontrolled muscle
spasm. It is used as a neurotoxin.

Morphine

It is a well-known pain killer and sedative drug. It acts through synaptic cleft and activates the mu-receptors on postsynaptic neurons.

Acetylcholine esterase inhibitors

These drugs decrease inhibit the acetylcholine enzyme present in the synaptic cleft. As a result, they prevent the degradation of acetylcholine. These drugs are classified as indirect-acting muscarinic agonists. They include physostigmine, pyridostigmine, neostigmine, etc.

Alcohol

Alcohol binds to GABA_A receptors an
increase the inhibitory effects of GABA. It also acts through the synaptic
cleft.

Conclusion/Summary

Synaptic cleft is a space between two neurons, connecting them to one another forming a synapse.

It is bound on one side by pre-synaptic neuron and
have post-synaptic neuron on the other side. The presynaptic neuron is always
an axon terminal. Depending on the type of synapse, the post-synaptic neuron
may be;

• An axon, as in axo-axonic synapse
• Dendrite in axo-dendritic synapse
  or
• Cell body or soma, as in
  axo-somatic synapses

When a nerve impulse reaches the presynaptic terminal, it causes release of neurotransmitters into the synaptic cleft. These neurotransmitters diffuse through the synaptic cleft and bind to the receptors on post-synaptic neurons.

This causes the transmission of nerve impulses from pre-synaptic to post-synaptic neuron.

Functions performed by synaptic cleft include;

• Diffusion of neurotransmitters
• Degradation of neurotransmitters
• Regulation of nerve impulse
  transmission
• Site of drug action

Alterations in nerve impulse transmission has been associated with a number of disorders including:

• Autism spectrum disorder
• Fragile X syndrome
• Alzheimer’s disease
• Addiction

Different drugs that can act through the synaptic
cleft include;

• Curare
• Morphine
• Strychnine
• Acetylcholine esterase inhibitors
• Alcohol

References

1. Squire, Larry
   R.; Floyd Bloom; Nicholas Spitzer (2008). Fundamental Neuroscience.
   Academic Press. pp. 425–6. ISBN 978-0-12-374019-9.
2. Garber, Steven
   D. (2002). Biology: A Self-Teaching Guide. John Wiley and Sons. p. 175. ISBN 978-0-471-22330-6.
3. Bear, Conners, Paradiso
   (2007). Neuroscience: exploring the brain. Philadelphia, PA: Lippincott
   Williams & Wilkins. pp. 113–118
4. Van Spronsen M,
   Hoogenraad CC. Synapse pathology in psychiatric and neurologic disease. Curr Neurol Neurosci Rep.
   2010;10(3):207–214. doi:10.1007/s11910-010-0104-8