Neurotransmitter

Neurotransmitters are chemical agents secreted at the end of axons of nerve cells that diffuse across the synaptic gap and transmit information to adjoining cells such as neurons, muscle cells, and glands , by altering their electrical state or activity. There are many neurotransmitters with a variety of structures and functions; two of the principle ones are acetylcholine and norepinephrine. Since the neurotransmitters convey information, anything that affects their behavior affects the function of the organism .

Function of neurotransmitters

The neurotransmitters are stored in tiny sac-like structures called vesicles at the end of axons. When an impulse, or nerve signal, reaches the end of the axon, the vesicles release a neurotransmitter into the small space between the adjoining cells (synaptic gap). Neurotransmitters diffuse across the synapse and bind to receptors in the receiving cell that are specific for the neurotransmitter. The kinds of reactions that occur in the receiving cell may vary. The cell may be excited and an action potential is set up and the impulse is transmitted; or the opposite effect may occur, and the cell will be inhibited from transmitting the impulse because it becomes hyperpolarized. Neurotransmitters function by changing the permeability of the cell membrane to various ions such as sodium and potassium. If an excess of sodium ions flow into the nerve cell, an impulse is generated. If an excess of potassium ions flow out, the impulse is inhibited. Sometimes the receiving cell receives a number of different messages at the same time, and they can cancel one another out. By their effects on the receiving cells, neurotransmitters coordinate behavior. The number and kind of neurotransmitter molecules received by the receptor cell, as well as the kind of receptor, determines whether the effect will be to stimulate or to inhibit. If neurotransmitters were allowed to operate over a long period of time, the results would be disastrous for the organism since there would be a constant overload of messages being sent. One way in which the problem is solved is through enzymes which break down the neurotransmitter very rapidly. One enzyme , acetylcholinesterase, can split one acetylcholine molecule every 40 microseconds. Many organic phosphates, which are poisons, operate by inhibiting acetylcholinesterase which leads to prolonged muscle contractions. Other neurotransmitters, such as norepinephrine and dopamine , are removed when they are taken up again by the vesicles in the axon endings after their release, or they are broken down by monamine oxidase. Some of the first anti-depressant drugs created were monoamine oxidase inhibitors (MAO inhibitors) such as phenelzine or tranylcypromine. MAO inhibitors inhibit the action of monoamine oxidase, thus allowing neurotransmitters, like norepinephrine, to have longer action. In this way, MAO inhibitor antidepressants are believed to alleviate symptoms of depression . Significant side effects resulting from the alteration of neurotransmitter degradation has led to a decline in the use of MAO inhibitors in the treatment of clinical depression.

Characteristics of neurotransmitters

The number of known neurotransmitters has increased tremendously over the past several years. One of the earliest ones studied was acetylcholine, the most common neurotransmitter found in both invertebrates and vertebrates . It is the stimulating agent for skeletal muscle cells, but is the inhibiting agent for heart muscle cells, which demonstrates that the action of a neurotransmitter is influenced by the target receptor cells. Norepinephrine, a catecholamine, is an example of a biogenic amine, which is derived from the amino acid tyrosine. It often works in an opposite way from acetylcholine in the autonomic nervous system and is also found in the cerebrum, cerebellum and spinal cord. Another catecholamine found in the brain is dopamine. It appears to be important in movement and regulating emotional responses. A widely distributed neurotransmitter, serotonin, is found in blood platelets, the lining of the digestive tract, and the brain. It causes very powerful contractions of smooth muscle, and is associated with mood, attention, emotions, and sleep . LSD and mescaline, psychoactive drugs, mimic the structure and function of serotonin and other biogenic drugs to change the mental state of the user. Some new anti-depression drugs, for example, allow lengthened serotonin activity. One very common drug, Prozac (Fluoxetine), is a selective serotonin re-uptake inhibitor (SSRI). As the name implies, the drug inhibits the re-uptake of serotonin neurotransmitter from synaptic gaps, thus increasing neurotransmitter action. In the brain, then, the increased serotonin activity alleviates depressive symptoms. One of the other amino acid derivatives, GABA (gamma-aminobutyric acid) is a major inhibitory transmitter in the central nervous system and it seems to play a role in Huntington's disease . In addition to the well known neurotransmitter, there are peptides, such as the opioids involved in killing pain and causing sleepiness, that act as neurotransmitters. Recently, certain gases, nitric oxide and carbon monoxide , have been discovered to be released from neurons. Nitric oxide has been found to diffuse to the nerves of the digestive system and govern the relaxation required for the normal movements of digestion.

Neurotransmitters and disease

Interest in the neurotransmitter is based on evidence that knowledge of how they function provides insight into the cause of some diseases, the effects of certain substances, and the behavior of organisms. Myasthenia gravis, which is a disease characterized by weakness of muscles and fatigue, is caused by a disturbance in the action of acetylcholine on skeletal muscles and is now treated by drugs that enhance the effect of acetylcholine. The discovery that dopamine-containing neurons in the brain of Parkinson's disease victims degenerate, which results in the shuffling gait and trembling characteristic of the disease, led to the use of levodopa, a compound that replaces dopamine.

Impairment of the dopamine system is also implicated in schizophrenia , a mental disease marked by disturbances in thinking and emotional reactions. Drugs, such as chlorpromazine and clozapine, that block dopamine receptors in the brain have been used to alleviate the symptoms and help patients return to a normal social setting. Depression, which afflicts about 3.5% of the population, is treated with antidepressants that affect norepinephrine and serotonin in the brain. The antidepressants help correct the abnormal excess or inhibition of signals that control mood, thoughts, pain, and other sensations. A new drug, fluoxetine, is a serotonin reuptake inhibitor which appears to establish the level of serotonin required to function at a normal level.

Alzheimer disease , which affects an estimated four million Americans, is characterized by memory loss and the eventual inability for self-care. The disease seems to be caused by a loss of cells in the basal forebrain which secrete acetylcholine. Some experimental drugs to alleviate the symptoms have been developed, but presently there is no known treatment for the disease.

Neurotransmitters and drugs

The rise of drug addiction has directed attention to the role of neurotransmitters by attempting to understand how it happens and how it can be counteracted. Cocaine and crack are psychostimulants that affect neurons containing dopamine in the limbic and frontal cortex of the brain; when they are used they generate a feelings of confidence and power. However, when large amounts are taken, people "crash" and suffer from physical and emotional exhaustion as well as depression. Opiates such as heroin and morphine appear to mimic naturally-occurring peptide substances in the brain with opiate activity called endorphins. Natural endorphins of the brain act to kill pain, cause sensations of pleasure, and cause sleepiness. Endorphins released with extensive aerobic exercise , for example, are responsible for the "rush" that long-distance runners experience.

It is believed that morphine and heroin combine with the endorphin receptors in the brain, resulting in reduced natural endorphin production. As a result, the drugs are needed to replace the naturally produced endorphins and addiction may occur. Attempts to counteract the effects involve using drugs that mimic them, such as nalorphine, naloxone, and naltrexone. One of the depressant drugs in widest use, alcohol , is believed to cause its effects by interacting with the GABA receptor. Initially anxiety is controlled, but greater amounts reduce muscle control and delay reaction time due to impaired thinking.

Neurotransmitters' role in memory and learning

One of the most exciting areas of research is the attempt to find out how learning and memory take place. One of the earliest researchers who attempted to explain learning and memory as a function of cellular change was the Canadian psychologist, Donald O. Hebb. He maintained that repeated firing of axons results in metabolic changes in the presynaptic and post synaptic neurons. In other words, learning produces lasting chemical changes in nerve cells.

Aplysia, a marine snail with only 20,000 relatively large neurons, has been used in studies to determine the biological basis of learning. A conditioned reflex in Apylsia has been shown to cause an increase in the release of a neurotransmitter that sets up a chain of reactions, one of which also increases the secretion of serotonin from a modulating neuron . In mammals , the hippocampus, part of the forebrain, stores long term memory for weeks before transferring it to the cerebral cortex. The transmitter used for long term potentiation is the amino acid, glutamate, which binds to receptors in the postsynaptic cell. This cell allows calcium to flow in and set up the activation of other molecules known as kinases. A growing body of evidence implicates the role of dopamine as one of the most important chemicals that regulate cell activity involved in working memory. Studies done with aged monkeys show that a deficiency in both dopamine and norepinephrine in the prefrontal cortex can induce a deficit in working memory. Injections of the deficient neurotransmitters restored memory function. Progress in deciphering the operation of the nervous system has helped to increase knowledge of the diverse role of the neurotransmitter.

See also Chemoreception.

Resources

books

BSCS Revision Team. Biological Science, A Molecular Approach. Lexington, MA: D.C. Heath & Co., 1990.

Campbell, Neil A. Biology. Menlo Park, CA: Benjamin/Cummings, 1987.

Campbell, N., J. Reece, and L. Mitchell. Biology. 5th ed. Menlo Park: Benjamin Cummings, Inc. 2000.

Carey, Joseph, ed. Brain Facts, A Primer on the Brain and theNervous System. Washington, DC: Society for Neuroscience, 1993.

Holtzman, Eric, and Alex B. Novikoff. Cells and Organelles. Philadelphia: Saunders College Publishing, 1984.

Kuffler, Stephen W., and John G. Nicholls. From Neuron toBrain. Sunderland, MA: Sinauer Associates, 1976.

Purves, Dale. Body and Brain, A Trophic Theory of Neural Connections. Cambridge, MA: Harvard University Press, 1988.

Raven, Peter H., and George B. Johnson. Biology. 3rd ed. St. Louis: Mosby Year Book, 1992.

periodicals

Fischbach, Gerald D. "Mind and Brain." Scientific American 3 (1992): 48-57.

Golden, Frederic. "Mental Illness: Probing the Chemistry of the Brain." Time 157 (January 2001).

Goldman-Rakic, Patricia S. "Working Memory and the Mind." Scientific American 3 (1992): 110-117.

LeDoux, Joseph E. "Emotion, Memory, and the Brain." Scientific American 6 (1994): 50-57.

Mary Finley

KEY TERMS

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Action potential

—A transient change in the electrical potential across a membrane which results in the generation of a nerve impulse.

Axon

—The threadlike projection of a neuron that carries an impulse away from the cell body of the neuron.

Catecholamine

—Monoamines such as the neurotransmitters norepinephrine, serotonin, and dopamine that are synthesized from the amino acid, tyrosine, and have similar structures.

Conditioned reflex

—A response in which one stimulus, the conditioned one, is associated with and elicits the same response as another stimulus, the unconditioned stimulus.

Dendrites

—Branched structures of nerve cell bodies which receive impulses from axons and carry them to the nerve cell body.

Limbic system

—Group of nuclei in the lower part of the forebrain involved in certain emotional and behavioral responses.

Monamine oxidase

—An enzyme found in the brain and liver which breaks down catecholamines such as norepinephrine, serotonin and dopamine.

Synapse

—Junction between cells where the exchange of electrical or chemical information takes place.

Working memory

—Memory that accesses and brings to mind information stored in longterm memory.