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===Nervous system===
===Nervous system===
Brain is made up of individual units: nerve cells and glial cells, which form the nervous system. Nervous system receives and interprets information about the internal and external environment of the body (Sensory System), makes decision about this information (Integrating System) and organizes and carries out action (Motor System).   
[[Brain]] is made up of individual units: [[nerve cell]]s and [[glial cell]]s, which form the [[nervous system]]. Nervous system receives and interprets information about the internal and external environment of the body (Sensory System), makes decision about this information (Integrating System) and organizes and carries out action (Motor System).   
===Neuron Doctrine===   
===Neuron Doctrine===   

Revision as of 17:35, 2 August 2006

1 Introduction

1.1 Nervous system

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

1.2 Neuron Doctrine

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 Morphology of the neuron

Neuron has four morphologically defined regions:

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

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 terminates at some 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 axons (an axo-axonal synapse). The space between the presynaptic and postsynaptic terminal is known as synaptic cleft.Two Types of synapses:

  1. Electrical Synapse: The information flows as direct, passive flow of current from one neuron to another. The current flows through specialized membrane channels that connect two cells called Gap junctions.
  2. Chemical Synapse: Nerve impulses are transmitted at synapses by the release of chemicals 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 site on the adjacent neuron causes an electrical reaction that facilitates the release of the neurotransmitter and its movement across the gap.

3 Types of neurotransmitters

Amino Acids: Some plain amino acids can work as neurotransmitters. For example, glutamate and glycine are both amino acids that are ordinarily used to build proteins. But in neurons, they can also get packaged into synaptic vesicles and get released as neurotransmitters.

Glutamate receptors typically mediate an excitatory response. 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 the spinal cord.

Monoamines: The term "monoamine" simply indicates a modified amino acid. 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 loss of motor skills.

Dopamine can also get modified further (in neurons that do not use it as a neurotransmitter) to get turned into epinephrine (also called adrenaline) and even norepinephrine and serotonin. All of these are then also "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.

Neurotransmitter 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 same 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, but we do not have to discuss them for our purposes.

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 causes calcium ion channels to open. 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 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-protein. Binding to the receptor leads to generation of excitatory or inhibitory post synaptic potentials (EPSP / IPSP) by closing and opening of specific ion channels.

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 back and forth across the neuron's membranes. This flow of ions makes the neuron's voltage rise toward zero. If enough excitatory receptors have been activated, the postsynaptic neuron responds by firing, generating a nerve impulse that causes its own neurotransmitter to be released into the next synapse. An inhibitory neurotransmitter causes different ions to pass back and forth across the postsynaptic neuron's membrane, lowering the nerve cell's voltage to -80 or -90 millivolts. 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 to contract. 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 presynaptic neuron clears the synapse of neurotransmitter molecules.

Retrieval of neurotransmitter

  1. 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.
  2. Cells known as astrocytes can remove neurotransmitters from the receptor area.
  3. 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.

Retrieval of Vesicular Membrane Membrane of the vesicles which fuses with the presynaptic terminal retrieves back by endocytosis of the same.

5 Role of Neurotransmitters in disease

Neurotransmitters are known to be involved in a number of disorders:
  1. 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.
  1. 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 masklike 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

  1. Many effective drugs have been shown to act by influencing neurotransmitter behavior. Some drugs work by interfering with the interactions between neurotransmitters and intestinal receptors. 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.
  2. 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.
  3. 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.

7 References

Principles of Neural Sciences, Eric Kandal

Specialties: Biology

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