Neurotransmitters and their Functions

A neurotransmitter is a chemical substance that is released from a nerve cell and then transmits an impulse from a nerve cell to its target. A target can be another nerve, muscle, organ, or other tissue.

It basically works as a messenger. They are
produced in the cell body of the neuron and transported to the axon terminal.
They are stored in vesicles.

Mechanism of action

Neurotransmitters have a specific mechanism of action. They are released from the presynaptic terminal. After release, they cause depolarization of the terminal membrane which ultimately causes activation of voltage-gated Ca2+ channels.

After activation of channels, there is an influx of Ca2+ ions which cause conformational changes. As a result, there is a fusion of the vesicle to the plasma membrane and there is the release of neurotransmitters at the synaptic cleft. (1).

Once released neurotransmitters diffuse through the synaptic cleft. There they normally bind to the specific receptors on the postsynaptic neuron membrane. The action potential is created at axon hillock and as a result, the neurotransmitter is released which then sends a message to its target.

After performing its function, neurotransmitter has different fates. It can diffuse out of the synaptic cleft, it may be taken the back up into presynaptic terminal through transporter molecules or enzymes metabolize it inside synaptic cleft.

Calcium (Ca2+) plays an important role in the process of neurotransmitter release. When Ca2+ channels are blocked, neurotransmitter release is inhibited. A neurotransmitter behaves in  2 ways: inhibitory or excitatory increases the chances of action potential generated. Inhibitory: decreases the chances of action potential generated.

Types of Neurotransmitter

The type of neurotransmitter depends on the type of synapses utilized.

The synaptic cleft, presynaptic terminal, and receiving dendrite of the next cell together form a junction known as the synapse (2).

There are different types of synapses but
they all transmit messages of two types.   

• Type I synapses: excitatory
• Type II synapses: inhibitory.

These types vary in appearance and location

Type I synapses:

• Location: Dendrite spine or shafts
• Characteristic feature: round synaptic vesicles
• Examples: Neurotransmitters that use these synapses are Acetylcholine Epinephrine,Glutamate, Histamine, dopamine

Type II synapses

• Location: cell body.
• Characteristic feature: flattened vesicles
• Examples: Some Neurotransmitters that use these synapses are Serotonin, GABA, Glycine.

The neurotransmitter release mechanisms are
impaired in many diseases like Schizophrenia, Depression, Alzheimer's disease

Neurotransmitter systems

Five major neurotransmitter systems are
operating in the brain.

• Acetylcholine system
• Dopamine system
• Noradrenaline system
• Histamine system
• Serotonin system

Functions of Neurotransmitters

Neurotransmitters play an important role in a wide variety of both physical and psychological functions. There are hundreds of neurotransmitters. Important ones are detailed here:

Norepinephrine is the main neurotransmitter of the sympathetic nervous system. It has two forms. It is also released as a hormone and causes blood vessels to contract and heart rate to increase. The basic function of norepinephrine as a neurotransmitter is to mobilize the brain and body for action.

It is responsible for fight and flight response . It plays an important role in wakefulness. It regulates circadian rhythm and feeding behavior. Along with dopamine, it plays a role in cognitive control and working memory.

It maintains energy homeostasis. It has a role in medullary control of respiration, negative emotional memory and perception of pain. It has a minor role in the reward center. Deficiency of norepinephrine can cause attention deficit hyperactivity disorder (ADHD), depression, and hypotension.

On the other hand, excess of norepinephrine can cause aches and pains, headache, tachycardia, palpitations, sweating, paleness, anxiety, and a drop in blood glucose. When sympathetic activity elevates for a long duration, it may cause weight loss (3).

Acetylcholine is the most abundant neurotransmitter in the human body found both in CNS and PNS. It causes muscles to contract thus playing a role in all movements of the body.

It activates pain responses and regulates endocrine and REM sleep functions. It is involved in regulating emotion, mood, learning, motivation and short-term memory. It plays a minor role in the reward center.

Low-level acetylcholine can lead to myasthenia gravis, which is characterized by muscle weakness.  Alzheimer's disease is characterized by memory loss and in later stages inability for self-care.

It is caused by a loss of cells that secrete acetylcholine in the basal forebrain. Excess of acetylcholine may cause signs and symptoms of both the nicotinic and muscarinic toxicity. All these include increased salivation, cramps, muscular weakness, lacrimation, muscular fasciculation, paralysis, blurry vision, and diarrhea.

Dopamine

Dopamine is the key neurotransmitter in our actions and relationships. It has a significant role in arousal, aversion, cognitive control, and working memory. It is involved in motivational salience, motor function, and control. It is a primary mediator of positive reinforcement and reward center. It is responsible for sexual arousal, orgasm, and refractory period.

Low levels of dopamine can cause Parkinson’s disease which is characterized by a tremor. Further distinguishing features are slow movements, rigid muscles, impaired posture and balance, loss of automatic movements, speech and writing changes.

It is caused by the loss of dopaminergic neurons in basal ganglia. Schizophrenia is another example. If there is an excess dopamine then it will lead to diseases like Tourette’s syndrome which is characterized by repetitive tics (4).

GABA

GABA (gamma-aminobutyric acid) is an inhibitory neurotransmitter that is present abundantly in the neurons of the cortex. The role of GABA is to inhibit the activity of the neurons. It plays a role in motor and cortical functions. It also regulates anxiety. Alcohol is believed to cause its effects by interacting with the GABA receptor.

Low levels of GABA can lead to
hyperactivity and causes conditions like epilepsy, seizures or mood
disorders.Excess GABA can lead to hypersomnia or daytime sleepiness.

GABA affects on the body are significant in
pharmacology as by increasing the level of GABA, we can treat epilepsy and calm
the trembling of people suffering from Huntington’s disease. Many medications
interact with GABA neurotransmission causing relaxation, pain relief,
stress, and anxiety reduction, lower blood pressure, and improved sleep (5).

Serotonin

Serotonin is an important neurotransmitter in the human body. It regulates mood, our social behavior, sleep, memory, and sexual desire. It is called the body's natural feel-good chemical.

Serotonin plays a role in bowel function.
Our intestines produce more serotonin if we eat something irritating or toxic
to our digestive system. The extra serotonin helps move the affected food along
so it’s expelled from our body quickly.

After an injury, platelets secrete
serotonin that causes vasoconstriction which helps in the blood-clotting
process (6).

Low levels of Serotonin can cause anxiety, depressed mood, aggression, impulsive behavior, suicidal thoughts, and insomnia. Generalized anxiety disorder involves an imbalance of serotonin.

High-level serotonin is associated with
osteoporosis. Excess serotonin can cause

Serotonin syndrome is characterized by restlessness,
confusion, tachycardia, and hypertension. A patient can present with dilated
pupils, loss of muscle coordination, muscle rigidity, heavy sweating, and diarrhea.

Serotonin is significant in pharmacology as
a major treatment of anxiety and depression is dependent on the use of
selective serotonin reuptake inhibitors. They inhibit the re-uptake of
serotonin from synaptic gaps and increase neurotransmitter action which in turn
alleviates depressive symptoms.

Glutamate

Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system. It helps in cognitive function, memory, and learning. Glutamate is a precursor for GABA. Glutamate plays an important role in brain development.

The brain appears to need glutamate to form
memories. Glutamate plays a significant role in muscle function. Glutamate
plays the main function in producing energy and the production of supporting glutathione
during exercise. Glutamate delay muscular dystrophy in animals deficient in
vitamin D.

Glutamate receptors are present on immune
cells (T cells, B cells, macrophages, and dendritic cells), which suggests that
glutamate plays a role in both innate and adaptive immunity.  Low brain levels of glutamate are associated
with neurological and psychiatric disorders. Glutamate levels were lower in
schizophrenic adults than healthy adults.

Low levels of glutamate results in lack
of energy, decreased appetite, pale skin, headaches, tingling or numbness in
the hands and feet, Insomnia, exhaustion and concentration problems. High
concentrations of glutamate in the brain have been associated with neurological
diseases such as schizophrenia, Parkinson's disease, multiple sclerosis,
Alzheimer's disease, stroke, and amyotrophic lateral sclerosis.

Endorphin

Endorphin is an important neurotransmitter. They are present in the whole nervous system but the majority is in the pituitary gland. They perform their actions by interacting with opioid receptors. They are of 3 types. Alpha endorphin, Beta-endorphin, Gamma endorphin.  They can be called stress relievers. .They alleviate pain and stress.

Deficiency of endorphins can cause depression and stress. Obsessive-compulsive disorders can also occur. Excess of endorphins can create feelings of euphoria, increased appetite, and sexual drive. Endorphins are important in pharmacology as most of the pain-killers act by mimicking the endorphin mechanism.

Conclusion

Neurotransmitters have a wide variety and mechanism of actions. They play a significant role in our daily activity both physical and psychological. Any impairment in their functions can lead to diseases.

References

1. https://www.d.umn.edu/~jfitzake/Lectures/DMED/NeuralCommunication/Neurotransmission/TransmitterRelease.html
2. https://www.britannica.com/science/neurotransmitter
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548657/
4. https://www.verywellmind.com/what-is-acetylcholine-2794810
5. https://thebrain.mcgill.ca/flash/i/i_01/i_01_m/i_01_m_ana/i_01_m_ana.html
6. https://www.verywellmind.com/what-is-serotonin-425327