Neurotransmitters

1 Introduction
2 Definition
3 Types of neurotransmitters
4 Mechanism of Action
5 Role of Neurotransmitters in disease
6 Pharmacology
7 References

1 Introduction

1.1 Nervous system

The brain is made up of individual units: nerve cells and glial cells, which form the nervous system. The nervous system receives and interprets information about the internal and external environment of the body (Sensory System), makes decisions about this information (Integrating System) and organizes and carries out action (Motor System).

1.2 Neuron Doctrine

The neuron doctrine holds that neurons are the basic signaling units of the nervous system and that each neuron is the discretely bounded cell whose several processes arise from its cell body.

1.3 Neuron morphology

A neuron has four morphologically defined regions:

Cell Body or Soma: consists of nucleus and perikaryon. It is the metabolic center of the neuron. It usually gives rise to two further processes: dendrites and axon. Its distinguishing feature is the presence of nissle granules.
Dendrites: The cell body gives rise to several processes, which typically branch out in a tree-like fashion. Dendrites serve as a main apparatus to receive inputs from other neurons.
Axon: The cell body is usually the origin of a tubular process that extends up to 1m. It is the main conducting unit of the neuron, capable of conveying information for great distances by propagating in an all-or-none way a transient electrical signal called an action potential. Axons are of two types: myelinated and non-myelinated.
Presynaptic Terminal: Near the ends, the axon divides into fine branches that have specialized swellings called presynaptic terminals. Through these terminals one neuron transmits information to another neuron via the resulting synapse.

1.4 Synaptic Transmission

Synaptic transmission refers to the propagation of nerve impulses from one nerve cell to another. This occurs at a specialized cellular structure known as the synapse, a junction at which the axon of the presynaptic neuron comes into extremely close proximity to a location upon the postsynaptic neuron. The end of a presynaptic axon, where it is juxtaposed to the postsynaptic neuron, is enlarged and forms a structure known as the terminal button. An axon can make contact anywhere along the second neuron: on the dendrites (an axodendritic synapse), the cell body (an axosomatic synapse) or the axon (an axo-axonal synapse). The space between the presynaptic and postsynaptic terminal is known as the synaptic cleft. There are two types of synapses:

Electrical Synapse: The information flows as the direct, passive flow of current from one neuron to another. The current flows through specialized membrane channels that connect two cells called gap junctions.
Chemical Synapse: Here the nerve impulses are transmitted at synapses by the release of chemical signaling agents called neurotransmitters. As a nerve impulse or action potential, reaches the end of a presynaptic axon, molecules of neurotransmitter are released into the synaptic cleft.

2 Definition

Neurotransmitters are chemicals that allow the movement of information from one neuron across the gap between it and the adjacent neuron. The release of neurotransmitters from one area of a neuron and the recognition of the chemicals by a receptor structure on the adjacent neuron typically causes an electrical reaction in the postsynaptic neuron.

3 Types of neurotransmitters

Amino Acids: Some simple amino acids can function as neurotransmitters. For example, glutamate and glycine are both amino acids that are ordinarily used to build proteins. But in some neurons, they can also get packaged into synaptic vesicles for eventual release as neurotransmitters.

Glutamate receptors typically mediate an excitatory response in the postsynaptic neuron. In fact, there are certain types of glutamate receptors that are thought to be involved in the learning process that occurs in our brains. Meanwhile, glycine receptors typically mediate an inhibitory response, for example, in specific areas of the spinal cord.

Monoamines: The term "monoamine" simply indicates an amino acid that has been modified in a specific manner. For example, the amino acid tyrosine gets modified through chemical reactions and is turned into dopamine. Dopamine is a monoamine that acts as a neurotransmitter. When someone has Parkinson's disease, the neurons that produce dopamine in the brain slowly degenerate, and that is a major cause of the loss of motor skills observed as the disease progresses.

Dopamine can also get modified further (in neurons that do not use it as a neurotransmitter) to become epinephrine (also called adrenaline), norepinephrine or serotonin. All of these substances are referred to as "monoamines."

Peptides: A peptide is a short chain of amino acids, not quite long enough to be considered a full-fledged protein. It has been noted that these peptide neurotransmitters can have complex effects on the postsynaptic neuron.

Many neurotransmittesr are known to cause the opening of a ligand-gated channel. But, some neurotransmitters, especially many of the peptides, don't necessarily work in that fashion. They can work through their own receptors to alter the way the ligand-gated channels of other neurotransmitters will work. This is why, they are known as neuromodulators.

Others: Acetylcholine and nitric oxide are just two other molecules that can be used by neurons as neurotransmitters, but don't fit into the categories listed above. There are many others as well.

4 Mechanism of Action

Within the cells, small-molecule neurotransmitter molecules are usually packaged in vesicles. When an action potential travels to the synapse, the rapid depolarization of the presynaptic membrane causes calcium ion channels to open and the intracellular level of calcium to increase. Calcium then stimulates the transport of vesicles to the synaptic membrane; the vesicle and cell membrane fuse, leading to the release of the packaged neurotransmitter, a mechanism called exocytosis.

The neurotransmitters then passively diffuse across the synaptic cleft to bind to receptors. The receptors are broadly classified into ionotropic and metabotropic receptors. Ionotropic receptors are ligand-gated ion channels that open or close through neurotransmitter binding. Metabotropic receptors, which can have a diverse range of effects on a cell, transduct the signal by secondary messenger systems, or G-proteins. Binding to the receptor leads to generation of excitatory or inhibitory postsynaptic potentials (EPSP / IPSP) through the closing and opening of specific ion channels in the postsynaptic membrane.

When a neuron is in its resting state, its voltage is about -70 millivolts. An excitatory neurotransmitter alters the membrane of the postsynaptic neuron, making it possible for ions (electrically charged molecules) to move across the neuron's membranes. This flow of ions makes the neuron's voltage rise toward zero (depolarization). If enough excitatory receptors have been activated, the postsynaptic neuron responds by firing, i.e. generating a nerve impulse, that causes its own neurotransmitter to be released into the next synapse.

An inhibitory neurotransmitter causes different ions to pass across the postsynaptic neuron's membrane, lowering the nerve cell's voltage to -80 or -90 millivolts (hyperpolarization). The drop in voltage makes it less likely that the postsynaptic cell will fire.

If the postsynaptic cell is a muscle cell rather than a neuron, an excitatory neurotransmitter will cause the muscle cell to generate a muscle twitch. If the postsynaptic cell is a gland cell, an excitatory neurotransmitter will cause the cell to secrete its contents.

While most neurotransmitters interact with their receptors to create new electrical nerve impulses that energize or inhibit the adjoining cell, some neurotransmitter interactions do not generate or suppress nerve impulses. Instead, they interact with a second type of receptor that changes the internal chemistry of the postsynaptic cell by either causing or blocking the formation of chemicals called second messenger molecules. These second messengers regulate the postsynaptic cell's biochemical processes and enable it to conduct the maintenance necessary to continue synthesizing neurotransmitters and conducting nerve impulses. Examples of second messengers, which are formed and entirely contained within the postsynaptic cell, include cyclic adenosine monophosphate (cAMP), diacylglycerol, and inositol phosphates.

Once neurotransmitters have been secreted into synapses and have passed on their chemical signals, the neurotransmitter molcules are cleared from the synaptic cleft, usually by either the presynaptic or the postsynaptic neuron.

Clearance of Neurotransmitters

Neurotransmitters can also be inactivated by degradation by a specific enzyme, for example, acetylcholine is broken down by the enzyme acetylcholinesterase into choline and acetate.
Cells known as astrocytes can remove neurotransmitters from the receptor area.
Neurotransmitters like dopamine, serotonin, and GABA are removed by a physical process called reuptake. In reuptake, a protein in the presynaptic membrane acts as a sort of sponge, causing the neurotransmitters to reenter the presynaptic neuron, where they can be broken down by enzymes or repackaged for reuse.

Fate of the Vesicular Membrane The membrane of the neurotransmitter-containing vesicles, which have fused with the presynaptic terminal and released the neurotransmitter molecules, is retrieved back into the presynaptic cell by endocytosis.

5 Role of Neurotransmitters in disease

Neurotransmitters are known to be involved in a number of disorders:

Alzheimer's disease: Victims of Alzheimer's disease suffer from loss of intellectual capacity, disintegration of personality, mental confusion, hallucinations, and aggressive – even violent – behavior. These symptoms are the result of progressive degeneration in many types of neurons in the brain. Forgetfulness, one of the earliest symptoms of Alzheimer's disease, is partly caused by the destruction of neurons that normally release the neurotransmitter acetylcholine. Medications that increase brain levels of acetylcholine have helped restore short-term memory and reduce mood swings in some Alzheimer's patients.

Parkinson's disease: Neurotransmitters also play a role in Parkinson's disease, which slowly attacks the nervous system, causing symptoms that worsen over time. Fatigue, mental confusion, a mask-like facial expression, stooping posture, shuffling gait, and problems with eating and speaking are among the difficulties suffered by Parkinson's victims. These symptoms have been partly linked to the deterioration and eventual death of neurons that run from the base of the brain to the basal ganglia, a collection of nerve cells that manufacture the neurotransmitter dopamine. The reasons why such neurons die are yet to be understood, but the related symptoms can be alleviated. L-dopa, or levodopa, widely used to treat Parkinson's disease, acts as a supplementary precursor for dopamine. It causes the surviving neurons in the basal ganglia to increase their production of dopamine, thereby compensating to some extent for the disabled neurons.

6 Pharmacology

Many effective drugs have been shown to act by influencing neurotransmitter behavior. Some drugs work by interfering with the interactions between neurotransmitters and receptors located in the intestinal tract. For example, belladonna decreases intestinal cramps in such disorders as irritable bowel syndrome by blocking acetylcholine from combining with receptors. This process reduces nerve signals to the bowel wall, which prevents painful spasms.
Other drugs block the reuptake process. One well-known example is the drug fluoxetine (Prozac), which blocks the reuptake of serotonin. Serotonin then remains in the synapse for a longer time, and its ability to act as a signal is prolonged, which contributes to the relief of depression and the control of obsessive-compulsive behaviors.
The actions of some drugs mimic those of naturally occurring neurotransmitters. The pain-regulating endorphins, for example, are similar in structure to heroin and codeine, which fill endorphin receptors to accomplish their effects. The wakefulness that follows caffeine consumption is the result of its blocking the effects of adenosine, a neurotransmitter that inhibits brain activity. Abnormalities in the production or functioning of certain neurotransmitters have been implicated in a number of diseases including Parkinson's disease, amyotrophic lateral sclerosis, and clinical depression.