THE UNDERLYING NATURE OF THOUGHT
RICHARD J.KOSCIEJEW
Neurophysiology is the study of how nerve cells, or neurons, receives and transmits information. Two types of phenomena are involved in processing nerve signals: Electrical and chemical. Electrical events propagate a signal within a neuron, and chemical processes transmit the signal from one neuron to another neuron or to a muscle cell.
A neuron is a long cell that has a thick central area containing the nucleus, it also has one long process called an axon and one or more short, bushy processes called dendrites. Dendrites receive impulses from other neurons. (The exceptions are sensory neurons, such as those that transmit information about temperature or touch, in which the signal is generated by specialized receptors in the skin.) These impulses are propagated electrically along the cell membrane to the end of the axon. At the tip of the axon the signal is chemically transmitted to an adjacent neuron or muscle cell.
Like all other cells, neurons contain charged ions: Potassium and sodium (positively charged) and chlorine (negatively charged). Neurons differ from other cells in that they are able to produce a nerve impulse. A neuron is polarized - that is, it has an overall negative charge inside the cell membrane because of the high concentration of chlorine ions and low concentration of potassium and sodium ions. The concentration of these same ions is exactly reversed outside the cell. This charge differential represents stored electrical energy, sometimes referred to as membrane potential or resting potential. The negative charge inside the cell is maintained by two features. The first is the selective permeability of the cell membrane, which is more permeable to potassium than sodium. The second feature is sodium pumps within the cell membrane that actively pump sodium out of the cell. When depolarization occurs, this charge differential across the membrane is reversed, and a nerve impulse is produced.
Depolarization is a rapid change in the permeability of the cell membrane. When sensory input or any other kind of stimulating current is received by the neuron, the membrane permeability is changed, allowing a sudden influx of sodium ions into the cell. The high concentration of sodium, or action potential, changes the overall charge within the cell from negative to positive. The local changes in ion concentration triggers similar reactions along the membrane, propagating the nerve impulse. After a brief period called the refractory period, during which the ionic concentration returned to resting potential, the neuron can repeat this process. Nerve impulses travel at different speeds, depending on the cellular composition of a neuron. Where speed of impulse is important, as in the nervous system, axons are insulated with a membranous substance called myelin. The insulation provided by myelin maintains the ionic charge over long distances. Nerve impulses are propagated at specific points along the myelin sheath; These points are called the nodes of Ranvier. Examples of myelinated axons are those in sensory nerve fibers and nerves connected to skeletal muscles. In non-myelinated cells, the nerve impulse is propagated more diffusely.
When the electrical signal reaches the tip of an axon, it stimulates small presynaptic vesicles in the cell. These vesicles contain chemicals called neurotransmitters, which are released into the microscopic space between neurons (the synaptic cleft). The neurotransmitter attaches on the surface of the adjacent neuron. This stimulus causes the adjacent cell to depolarize and propagate an action potential of its own. The duration of a stimulus from a neurotransmitter is limited by the breakdown of the chemicals in the synaptic cleft and the reuptake by the neuron that produced them. Formerly, each neuron was thought to make only one transmitter, but recent studies have shown that some cells make two or more.
During the early 1900s, in examining the workings of the nervous system, physiologists were beginning to explore the idea that the transmission of nerve impulses takes place, in part, via chemical means. Loewi decided to explore this idea. During a stay in London in 1903, he met Sir Dale, who was also interested in the chemical transmission of nerve impulses. However, for Loewi, Dale, and all the other researchers pursuing a chemical transmitter of nerve impulses, years of effort produced no solid evidence. In 1921 Loewi suspended two frogs' hearts in solution, one with a major nerve removed. Removing fluid from the heart that still contained the nerve, and injecting the fluid into the nerveless heart, Loewi observed that the second heart behaved as if the missing nerve were present. The nerves, he concluded, do not act directly on the heart - it is the action of chemicals, freed by the stimulation of nerves, that causes increases in heart rate and other functional changes. In 1926 Loewi and his colleagues identified one of the chemicals in his experiment as acetylcholine. This was indisputably a neurotransmitter - a chemical that serves to transmit nerve impulses in the involuntary nervous system.
Neurotransmitter
We acknowledge the neurotransmitters are inherently made by chemically induced neurons, or nerve cells. Neurons send out neurotransmitters as chemical signals to activate or inhibit the function of neighboring cells.
Within the central nervous system, which consists of the brain and the spinal cord, neurotransmitters pass from neuron to neuron. In the peripheral nervous system, which is made up of the nerves that run from the central nervous system to the rest of the body, the chemical signals pass between a neuron and an adjacent muscle or gland cells.
Chemical compounds - belonging to three chemical families - are widely recognized as neurotransmitters. In addition, certain other body chemicals, including adenosine, histamine, enkephalins, endorphins, and epinephrine, have neurotransmitterlike properties. Experts believe that there are many more neurotransmitters as yet undiscovered.
The first of the three families is composed of amines, a group of compounds containing molecules of carbon, hydrogen, and nitrogen. Among the amine neurotransmitters are acetylcholine, norepinephrine, dopamine, and serotonin. Acetylcholine is the most widely used neurotransmitter in the body, and neurons that leave the central nervous system (for example, those running to skeletal muscle) use acetylcholine as their neurotransmitter; neurons that run to the heart, blood vessels, and other organs may use acetylcholine or norepinephrine. Dopamine is involved in the movement of muscles, and it controls the secretion of the pituitary hormone prolactin, which triggers milk production in nursing mothers.
The second neurotransmitter family is composed of amino acids, organic compounds containing both an amino group (NH2) and a carboxylic acid group (COOH). Amino acids that serve as neurotransmitters include glycine, glutamic and aspartic acids, and gamma-amino butyric acid (GABA). Glutamic acid and GABA are the most abundant neurotransmitters within the central nervous system, and especially in the cerebral cortex, which is largely responsible for such higher brain functions as thought and interpreting sensations.
The third neurotransmitter family is composed of peptides, which are compounds that contain at least two, and sometimes as many as 100 amino acids. Peptide neurotransmitters are poorly understood, but scientists know that the peptide neurotransmitter called substance P influences the sensation of pain.
In general, each neuron uses only a single compound as its neurotransmitter. However, some neurons outside the central nervous system are able to release both an amine and a peptide neurotransmitter.
Neurotransmitters are manufactured from precursor compounds like amino acids, glucose, and the dietary amine-called choline. Neurons modify the structure of these precursor compounds in a series of reactions with enzymes. Neurotransmitters that comes from amino acids include serotonin, for which it is derived from tryptophan. Dopamine and norepinephrine, under which are derived from tyrosine, and glycine, which is derived from threonine. Among the neurotransmitters made from glucose are glutamate, aspartate, and GABA. Choline serves as the precursor for acetylcholine
Neurotransmitters are released into a microscopic gap, called a synapse, that separates the transmitting neuron from the cell receiving the chemical signal. The cell that generates the signal is called the presynaptic cell, while the receiving cell is termed the postsynaptic cell.
After their release into the synapse, neurotransmitters combine chemically with highly specific protein molecules, termed receptors, that are embedded in the surface membranes of the postsynaptic cell. When this combination occurs, the voltage, or electrical force, of the postsynaptic cell is either increased (excited) or decreased (inhibited).
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, 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. For example, acetylcholine is broken down by the enzyme acetylcholinesterase into choline and acetate. Neurotransmitters like dopamine, serotonin, and GABA is 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.
Neurotransmitters are known to be involved in a number of disorders, including 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.
Neurotransmitters also play a role in Parkinson 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 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 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.
Many other 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.
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.
Dopamine
Dopamine, chemical known as a neurotransmitter essential to the functioning of the central nervous system. In the process of neurotransmission, dopamine is transferred from one nerve cell, or neuron, to another, playing a key role in brain function and human behavior.
Dopamine forms from a precursor molecule called dopa, which is manufactured in the liver from the amino acid tyrosine. Dopa is then transported by the circulatory system to neurons in the brain, where the conversion to dopamine takes place.
Dopamine is a versatile neurotransmitter. Among its many functions, it plays a major role in two activities of the central nervous system: one that helps control movement, and a second that is strongly associated with emotion-based behaviors.
The pathway involved in movement control is called the nigrostriatal pathway. Dopamine is released by neurons that originate from an area of the brain called the substantia nigra and connect to the part of the brain known as the corpora striata, an area known to be important in controlling the musculoskeletal system.
The second brain pathway in which dopamine plays a major role is called the mesocorticolimbic pathway. Neurons in an area of the brain called the ventral tegmentalarea transmits dopamine to other neurons connected to various parts of the limbic system, which is responsible for regulating emotion, motivation, behavior, the sense of smell, and various autonomic, or involuntary, functions like heartbeat and breathing.A growing body of evidence suggests that dopamine is involved in several major brain disorders. Narcolepsy, a disorder characterized by brief, recurring episodes of sudden, deep sleep, is associated with abnormally high levels of both dopamine and a second neurotransmitter, acetylcholine. Huntington’s chorea, an inherited, fatal illness in which neurons in the base of the brain are progressively destroyed, is also linked to an excess of dopamine.
Commonly known as shaking palsy, Parkinson disease is another brain disorder in which dopamine is involved. Besides tremors of the limbs, Parkinson patients suffer from muscular rigidity, which leads to difficulties in walking, writing, and speaking. This disorder results from the degeneration and death of neurons in the nigrostriatal pathway, resulting in low levels of dopamine. The symptoms of Parkinson disease can be minimized by treatment with a drug called levodopa, or L-dopa, which converts to dopamine in the brain.
Schizophrenia is a psychiatric disorder characterized by loss of contact with reality and major changes in personality. Schizophrenics have normal levels of dopamine in the brain, but because they are highly sensitive to this neurotransmitter, these normal levels of dopamine triggers unusual behaviors. Drugs such as thorazine that blocks the action of dopamine have been found to decrease the symptoms of schizophrenia.
Studies indicate that people who are addicted to alcohol and other drugs like, cocaine and nicotine have less dopamine in the mesocorticolimbic pathway. These drugs appear to increase dopamine levels, resulting in the pleasurable feelings associated with the drugs.
Serotonin
Serotonin, neurotransmitter, or chemical that transmits messages across the synapses, or gaps, between adjacent cells. Among its many functions, serotonin is released from blood cells called platelets to activate blood vessel constriction and blood clotting. In the gastrointestinal tract, serotonin inhibits gastric acid production and stimulates muscle contraction in the intestinal wall. Its functions in the central nervous system and effects on human behavior - including mood, memory, and appetite control - have been the subject of a great deal of research. This intensive study of serotonin has revealed important knowledge about the serotonin-related cause and treatment of many illnesses.
Serotonin is produced in the brain from the amino acid tryptophan, which is derived from foods high in protein, such as meat and dairy products. Tryptophan is transported to the brain, where it is broken down by enzymes to produce serotonin. In the process of neurotransmission, serotonin is transferred from one nerve cell, or neuron, to another, triggering an electrical impulse that stimulates or inhibits cell activity as needed. Serotonin is then reabsorbed by the first neuron, in a process known as reuptake, where it is recycled and used again or converted into an inactive chemical form and excreted.
While the complete picture of serotonin’s function in the body is still being investigated, many disorders are known to be associated with an imbalance of serotonin in the brain. Drugs that manipulate serotonin levels have been used to alleviate the symptoms of serotonin imbalances. Some of these drugs, known as selective serotonin reuptake inhibitors (SSRIs), block or inhibit the reuptake of serotonin into neurons, enabling serotonin to remain active in the synapses for a longer period of time. These medications are used to treat such psychiatric disorders as depression; Obsessive-compulsive disorder, in which repetitive and disturbing thoughts trigger bizarre, ritualistic behaviors, and impulsive aggressive behaviors. Fluoxetine (more commonly known by the brand name Prozac), is a widely prescribed SSRI used to treat depression, and more recently, obsessive-compulsive disorder.
Drugs that affect serotonin levels may prove beneficial in the treatment of nonpsychiatric disorders as well, including diabetic neuropathy (degeneration of nerves outside the central nervous system in diabetics) and premenstrual syndrome. Recently the serotonin-releasing agent dexfenfluramine has been approved for patients who are 30 percent or more over their ideal body weight. By preventing serotonin reuptake, dexfenfluramine promotes satiety, or fullness, after eating less food.
Other drugs serve as agonists that react with neurons to produce effects similar to those of serotonin. Serotonin agonists have been used to treat migraine headaches, in which low levels of serotonin cause arteries in the brain to swell, resulting in a headache. Sumatriptan is an agonist drug that mimics the effects of serotonin in the brain, constricting blood vessels and alleviating pain.
Drugs known as antagonists bind with neurons to prevent serotonin neurotransmission. Some antagonists have been found effective in treating the nausea that typically accompanies radiation and chemotherapy in cancer treatment. Antagonists are also being tested to treat high blood pressure and other cardiovascular disorders by blocking serotonin’s ability to constrict blood vessels. Other antagonists may produce an effect on learning and memory in age-associated memory impairment.
The Synapse
The Synapse is the signals conveying everything that human beings sense and think, and every motion they make, follows nerve pathways in the human body as waves of ions (atoms or groups of atoms that carry electric charges). Australian physiologist Sir John Eccles discovered many of the intricacies of this electrochemical signaling process, particularly the pivotal step in which a signal is conveyed from one nerve cell to another. He shared the 1963 Nobel Prize in physiology or medicine for this work, which he described in a 1965 Scientific American article.
How does one nerve cell transmit the nerve impulse to another cell? Electron microscopy and other methods show that it does so by means of special extensions that deliver a squirt of transmitter substance
The human brain is the most highly organized form of matter known, and in complexity the brains of the other higher animals are not greatly inferior. For certain purposes it is expedient to regard the brain as being analogous to a machine. Even if it is so regarded, however, it is a machine of a totally different kind from those made by man. In trying to understand the workings of his own brain man meets his highest challenge. Nothing is given; There are no operating diagrams, no maker's instructions.
The first step in trying to understand the brain is to examine its structure in order to discover the components from which it is built and how they are related to each another. After that one can attempt to understand the mode of operation of the simplest components. These two modes of investigation - the morphological and the physiological - have now become complementary. In studying the nervous system with today's sensitive electrical device, however, it is all too easy to find physiological events that cannot be correlated with any known anatomical structure. Conversely, the electron microscope reveals many structural details whose physiological significance is obscure or unknown.
At the close of the past century the Spanish anatomist Santiago Ramón Cajal showed how all parts of the nervous system are built up of individual nerve cells of many different shapes and sizes. Like other cells, each nerve cell has a nucleus and the surrounding cytoplasm. Its outer surface consists of numerous fine branches - the dendrites - that receive nerve impulses from other nerve cells, and one relatively long branch - the axon - that transmits nerve impulses. Near its end the axon divides into branches that terminate at the dendrites or bodies of other nerve cells. The axon can be as short as a fraction of a millimeter or as long as a meter, depending on its place and function. It has many of the properties of an electric cable and is uniquely specialized to conduct the brief electrical waves called nerve impulses. In very thin axons these impulses travel at less than one meter per second; In others, for example in the large axons of the nerve cells that activate muscles, they travel as fast as 100 meters per second.
The electrical impulse that travels along the axon ceases abruptly when it comes to the point where the axon's terminal fibers make contact with another nerve cell. These junction points were given the name "synapses" by Sir Charles Sherrington, who laid the foundations of what is sometimes called synaptology. If the nerve impulse is to continue beyond the synapse, it must be regenerated afresh on the other side. As recently as 15 years ago some physiologists held that transmission at the synapse was predominantly, if not exclusively, an electrical phenomenon. Now, however, there is abundant evidence that transmission is effectuated by the release of specific chemical substances that trigger a regeneration of the impulse. In fact, the first strong evidence showing that some transmitter substance acts across the synapse was provided more than 40 years ago by Sir Henry Dale and Otto Loewi.
It has been estimated that the human central nervous system, which of course includes the spinal cord as well as the brain itself, consists of about 10 billion (1010) nerve cells. With rare exceptions each nerve cell receives information directly in the form of impulses from many other nerve cells - often hundreds - and transmits information to a like number. Depending on its threshold of response, a given nerve cell may fire an impulse when stimulated by only a few incoming fibers or it may not fire until stimulated by many incoming fibers. It has long been known that this threshold can be raised or lowered by various factors. Moreover, it was conjectured some 60 years ago that some of the incoming fibers must inhibit the firing of the receiving cell rather than excite it. The conjecture was subsequently confirmed, and the mechanism of the inhibitory effect has now been clarified. This mechanism and its equally fundamental counterpart - nerve-cell excitation - are of its topic.
At the level of anatomy there are some clues to indicate how the fine axon terminals impinging on a nerve cell can make the cell regenerate a nerve impulse of its own nerve cell and its dendrites are covered by fine branches of nerve fibers that terminate in knoblike structures. These structures are the synapses.
The electron microscope has revealed structural details of synapses that fit in nicely with the view that a chemical transmitter is involved in nerve transmission. Enclosed in the synaptic knob are many vesicles, or tiny sacs, which appear to contain the transmitter substances that induce synaptic transmission. Between the synaptic knob and the synaptic membrane of the adjoining nerve cell is a remarkably uniform space of about 20 millimicrons that is termed the synaptic cleft. Many of the synaptic vesicles are concentrated adjacent to this cleft; It seems plausible that the transmitter substance is discharged from the nearest vesicles into the cleft, where it can act on the adjacent cell membrane. This hypothesis is supported by the discovery that the transmitter is released in packets of a few thousand molecules.
The study of synaptic transmission was revolutionized in 1951 by the introduction of delicate techniques for recording electrically from the interior of single nerve cells. This is done by inserting into the nerve cell an extremely fine glass pipette with a diameter of .5 microns - about a fifty-thousandth of an inch. The pipette is filled with an electrically conducting salt solution such as concentrated potassium chloride. If the pipette is carefully inserted and held rigidly in place, the cell membrane appears to seal quickly around the glass, thus preventing the flow of a short-circuiting current through the puncture in the cell membrane. Impaled in this fashion, nerve cells can function normally for hours. Although there is no way of observing the cells during the insertion of the pipette, the insertion can be guided by using as clues the electric signals that the pipette picks up when close to active nerve cells.
At the John Curtin School of Medical Research in Canberra first employed this technique, choosing to study the large nerve cells called motoneurons, which lie in the spinal cord and whose function is to activate muscles. This was a fortunate choice: Intracellular investigations with motoneurons have proved to be easier and more rewarding than those with any other kind of mammalian nerve cell.
Finding that when the nerve cell responds to the chemical synaptic transmitter, the response depends in part on characteristic features of ionic composition that are also concerned with the transmission of impulses in the cell and along its axon. When the nerve cell is at rest, its physiological makeup resembles that of most other cells in that the water solution inside the cell is quite different in composition from the solution in which the cell is bathed. The nerve cell is able to exploit this difference between external and internal composition and use it in quite different ways for generating an electrical impulse and for synaptic transmission.
The composition of the external solution is well established because the solution is essentially the same as blood from which cells and proteins have been removed. The composition of the internal solution is known only approximately. Indirect evidence indicates that the concentrations of sodium and chloride ions outside the cell are respectively some 10 and 14 times higher than the concentrations inside the cell. In contrast, the concentration of potassium ions inside the cell is about 30 times higher than the concentration outside.
How can one account for this remarkable state of affairs? Part of the explanation is that inside of the cell is negatively charged with the respect of the cell by about 70 millivolts. Since like charges repel each other, this internal negative charge tends to drive chloride ions (Cl-) outward through the cell membrane and, at the same time, to impede their inward movement. In fact, a potential difference of 70 millivolts is just sufficient to maintain the observed disparity in the concentration of chloride ions inside the cell and outside it; Chloride ions diffuse inward and outward at equal rates. A drop of 70 millivolts across the membrane therefore defines the "equilibrium potential" for chloride ions.
To obtain a concentration of potassium ions (K) that is 30 times higher inside the cell than outside would require that the interior of the cell membrane be about 90 millivolts negative with respect to the exterior. Since the actual interior is only 70 millivolts negative, it falls short of the equilibrium potential for potassium ions by 20 millivolts. Evidently the thirtyfold concentration can be achieved and maintained only if there is some auxiliary mechanism for "pumping" potassium ions into the cell at a rate equal to their spontaneous net outward diffusion.
The pumping mechanisms have fewer or some more difficult tasks of pumping sodium ions (Na) out of the cell against a potential gradient of 130 millivolts. This figure is obtained by adding the 70 millivolts of internal negative charge to the equilibrium potential for sodium ions, which is 60 millivolts of internal positive charge. If it were not for this postulated pump, the concentration of sodium ions inside and outside the cell would be almost the reverse of what is observed.
In their classic studies of nerve-impulse transmission in the giant axon of the squid, A. L. Hodgkin, A. F. Huxley and Bernhard Katz of Britain demonstrated that the propagation of the impulse coincides with abrupt changes in the permeability of the axon membrane. When a nerve impulse has been triggered in some way, what can be described as a gate opens and lets sodium ions pour into the axon during the advance of the impulse, making the interior of the axon locally positive. The process is self-reinforcing in that the flow of some sodium ions through the membrane opens the gate further and makes it easier for others to follow. The sharp reversal of the internal polarity of the membrane constitutes the nerve impulse, which moves like a wave until it has traveled the length of the axon. In the wake of the impulse the sodium gate closes and a potassium gate opens, thereby restoring the normal polarity of the membrane within a millisecond or less.
With this understanding of the nerve impulse in hand, one is ready to follow the electrical events at the excitatory synapse. One might guess that if the nerve impulse results from an abrupt inflow of sodium ions and a rapid change in the electrical polarity of the axon's interior, something similar must happen at the body and dendrites of the nerve cell in order to generate the impulse in the first place. Indeed, the function of the excitatory synaptic terminals on the cell body and its dendrites is to depolarize the interior of the cell membrane essentially by permitting an inflow of sodium ions. When the depolarization reaches a threshold value, a nerve impulse is triggered.
As a simple instance of this phenomenon we have recorded the depolarization that occurs in a single motoneuron activated directly by the large nerve fibers that enter the spinal cord from special stretch-receptors known as annulospiral endings. These receptors in turn are located in the same muscle that is activated by the motoneuron under study. Thus the whole system forms a typical reflex arc, such as the arc responsible for the patellar reflex, or "knee jerk."
To conduct the experiment we anesthetize an animal (most often a cat) and free by dissection a muscle nerves that contains these large nerve fibers. By applying a mild electric shock to the exposed nerve one can produce a single impulse in each of the fibers; Since the impulses travel to the spinal cord almost synchronously they are referred to collectively as a volley. The number of impulses contained in the volley can be reduced by reducing the stimulation applied to the nerve. The volley strength is measured at a point just outside the spinal cord and is displayed on an oscilloscope. About half a millisecond after detection of a volley there is a wavelike change in the voltage inside the motoneuron that has received the volley. The change is detected by a microelectrode inserted in the motoneuron and is displayed on another oscilloscope.
What we find is that the negative voltage inside the cell becomes progressively fewer negative as more of the fibers impinging on the cell are stimulated to fire. This observed depolarization is in fact a simple summation of the depolarizations produced by each individual synapse. When the depolarization of the interior of the motoneuron reaches a critical point, a "spike" suddenly appears on the second oscilloscope, showing that a nerve impulse has been generated. During the spike the voltage inside the cell changes from about 70 millivolts negative to as much as 30 millivolts positive. The spike regularly appears when the depolarization, or reduction of membrane potential, reaches a critical level, which is usually between 10 and 18 millivolts. The only effect of a further strengthening of the synaptic stimulus is to shorten the time needed for the motoneuron to reach the firing threshold. The depolarizing potentials produced in the cell membrane by excitatory synapses are called excitatory postsynaptic potentials, or EPSP's.
Through one barrel of a double-barreled microelectrode one can apply a background current to change the resting potential of the interior of the cell membrane, either increasing it or decreasing it. When the potential is made more negative, the EPSP rises more steeply to an earlier peak. When the potential is made less negative, the EPSP rises more slowly to a lower peak. Finally, when the charge inside the cell is reversed so as to be positive with respect to the exterior, the excitatory synapses give rise to an EPSP that is actually the reverse of the normal one.
These observations support the hypothesis that excitatory synapses produce what amounts virtually to a short circuit in the synaptic membrane potential. When this occurs, the membrane no longer acts as a barrier to the passage of ions but lets them flow through in response to the differing electric potential on the two sides of the membrane. In other words, the ions are momentarily allowed to travel freely down their electrochemical gradients, which means that the sodium ions flow into the cell and, to a lesser degree, potassium ions flow out. It is this net flow of positive ions that creates the excitatory postsynaptic potential. The flow of negative ions, such as the chloride ion, is apparently not involved. By artificially altering the potential inside the cell one can establish that there is no flow of ions, and therefore no EPSP, when the voltage drop across the membrane is zero.
How is the synaptic membrane converted from a strong ionic barrier into an ion-permeable state? It is currently accepted that the agency of conversion is the chemical transmitter substance contained in the vesicles inside the synaptic knob. When a nerve impulse reaches the synaptic knob, some of the vesicles are caused to eject the transmitter substance into the synaptic cleft. The molecules of the substance would take only a few microseconds to diffuse across the cleft and become attached to specific receptor sites on the surface membrane of the adjacent nerve cell.
Presumably the receptor sites are associated with fine channels in the membrane that are opened in some way by the attachment of the transmitter-substance molecules to the receptor sites. With the channels thus opened, sodium and potassium ions flow through the membrane thousands of times more readily than they normally do, thereby producing the intense ionic flux that depolarizes the cell membrane and produces the EPSP. In many synapses the current flows strongly for only about a millisecond before the transmitter substance is eliminated from the synaptic cleft, either by diffusion into the surrounding regions or as a result of being destroyed by enzymes. The latter process is known to occur when the transmitter substance is acetylcholine, which is destroyed by the enzyme acetylcholinesterase.
The substantiation of this general picture of synaptic transmission requires the solution of many fundamental problems. Since we do not know the specific transmitter substance for the vast majority of synapses in the nervous system we do not know if there are many different substances or only a few. The only one identified with reasonable certainty in the mammalian central nervous system is acetylcholine. We know practically nothing about the mechanism by which a presynaptic nerve impulse causes the transmitter substance to be injected into the synaptic cleft. Nor do we know how the synaptic vesicles not immediately adjacent to the synaptic cleft ensue to moved up to the firing line to replace the emptied vesicles. It is conjectured that the vesicles contain the enzyme systems needed to recharge themselves. The entire process must be swift and efficient: the total amount of transmitter substance in synaptic terminals is enough for only a few minutes of synaptic activity at normal operating rates. There are also knotty problems to be solved on the other side of the synaptic cleft. What, for example, is the nature of the receptor sites? How are the ionic channels in the membrane opened up?
The second type of synapse that has been identified in the nervous system. These are the synapses that can inhibit the firing of a nerve cell even though it may be receiving a volley of excitatory impulses. When inhibitory synapses are examined in the electron microscope, they look very much like excitatory synapses. (There are probably some subtle differences, but they need not concern us here.) Microelectrode recordings of the activity of single motoneurons and other nerve cells have now shown that the inhibitory postsynaptic potential (IPSP) is virtually a mirror image of the EPSP. Moreover, individual inhibitory synapses, like excitatory synapses, have a cumulative effect. The chief difference is simply that the IPSP makes the cell's internal voltage more negative than it is normally, which is in a direction opposite to that needed for generating a spike discharge.
By driving the internal voltage of a nerve cell in the negative direction inhibitory synapses oppose the action of excitatory synapses, which of course drive it in the positive direction. Hence if the potential inside a resting cell is 70 millivolts negative, a strong volley of inhibitory impulses can drive the potential to 75 or 80 millivolts depreciating count. One can easily see that if the potential is made more negative in this way the excitatory synapses find it more difficult to raise the internal voltage to the threshold point for the generation of a spike. Thus, the nerve cell responds to the algebraic sum of the internal voltage changes produced by excitatory and inhibitory synapses.
If, as in the experiment described earlier, the internal membrane potential is altered by the flow of an electric current through one barrel of a double-barreled microelectrode, one can observe the effect of such changes on the inhibitory postsynaptic potential. When the internal potential is made less negative, the inhibitory postsynaptic potential is deepened. Conversely, when the potential is made more negative, the IPSP diminishes; it finally reverses when the internal potential is driven below minus 80 millivolts.
One can therefore assume that inhibitory synapse’s share with excitatory synapses the ability to change the ionic permeability of the synaptic membrane. The difference is that inhibitory synapses enable ions to flow freely down an electrochemical gradient that has an equilibrium point at minus 80 millivolts rather than at zero, as is the case for excitatory synapses. This effect could be achieved by the outward flow of positively charged ions such as potassium or the inward flow of negatively charged ions such as chloride, or by a combination of negative and positive ionic flows such that the interior reaches equilibrium at minus 80 millivolts.
If the concentration of chloride ions within the cell is increased as much as three times, the inhibitory postsynaptic potential reverses and acts as a depolarizing current; that is, it resembles an excitatory potential. On the other hand, if the cell is heavily injected with sulfate ions, which are also negatively charged, there is no such reversal. This simple test shows that under the influence of the inhibitory transmitter substance, which is still unidentified, the subsynaptic membrane becomes permeable momentarily to chloride ions but not to sulfate ions. During the generation of the IPSP the outflow of chloride ions is so rapid that it more than outweighs the flow of other ions that generate the normal inhibitory potential.
The effect of injecting motoneurons with more than 30 kinds of negatively lunged ion. With one exception the hydrated ions (ions bound to water) to which the cell membrane is permeable under the influence of the inhibitory transmitter substance are smaller than the hydrated ions to which the membrane is impermeable. The exception is the formate ion (HCO2-), which may have an ellipsoidal shape and so be able to pass through membrane pores that block smaller spherical ions.
Apart from the formate ion all the ions to which the membrane is permeable have a diameter not greater than 1.14 times the diameter of the potassium ion; That is, they are less than 2.9 angstrom units in diameter. Comparable investigations in other laboratories have found the same permeability effects, including the exceptional behavior of the formate ion, in fishes, toads and snails. It may well be that the ionic mechanism responsible for synaptic inhibition is the same throughout the animal kingdom.
The significance of these and other studies is that they strongly indicate that the inhibitory transmitter substance opens the membrane to the flow of potassium ions but not to sodium ions. It is known that the sodium ion is somewhat larger than any of the negatively charged ions, including the formate ion, that are able to pass through the membrane during synaptic inhibition. It is not possible, however, to test the effectiveness of potassium ions by injecting excess amounts into the cell because the excess is immediately diluted by an osmotic flow of water into the cell.
The concentration of potassium ions inside the nerve cell is about 30 times greater than the concentration outside, and to maintain this large difference in concentration without the help of some metabolic pumps inside of the membrane would have to be charged 90 millivolts negative with respect to the exterior. This implies that if the membrane were suddenly made porous to potassium ions, the resulting outflow of ions would make the inside potential of the membrane even more negative than it is in the resting state, and that is just what happens during synaptic inhibition. The membrane must not simultaneously become porous to sodium ions, because they exist in much higher concentration outside the cell than inside and their rapid inflow would more than compensate for the potassium outflow. In fact, the fundamental difference between synaptic excitation and synaptic inhibition is that the membrane freely passes sodium ions in response to the former and largely excludes the passage of sodium ions in response to the latter.
This fine discrimination between ions that are not very different in size must be explained by any hypothesis of synaptic action. It is most unlikely that the channels through the membrane are created afresh and accurately maintained for a thousandth of a second every time a burst of transmitter substance is released into the synaptic cleft. It is more likely that channels of at least two different sizes are built directly into the membrane structure. In some way the excitatory transmitter substance would selectively unplug the larger channels and permit the free inflow of sodium ions. Potassium ions would simultaneously flow out and thus would tend to counteract the large potential change that would be produced by the massive sodium inflow. The inhibitory transmitter substance would selectively unplug the smaller channels that are large enough to pass potassium and chloride ions but not sodium ions.
To explain certain types of inhibition other features must be added to this hypothesis of synaptic transmission. In the simple hypothesis chloride and potassium ions can flow freely through pores of all inhibitory synapses. It has been shown, however, that the inhibition of the contraction of heart muscle by the vagus nerve is due almost exclusively to potassium-ion flow. On the other hand, in the muscles of crustaceans and in nerve cells in the snail's brain synaptic inhibition is due largely to the flow of chloride ions. This selective permeability could be explained if there were fixed charges along the walls of the channels. If such charges were negative, they would repel negatively charged ions and prevent their passage; if they were positive, they would similarly prevent the passage of positively charged ions. One can now suggest that the channels opened by the excitatory transmitter are negatively charged and so do not permit the passage of the negatively charged chloride ion, even though it is small enough to move through the channel freely.
One might wonder if a given nerve cell can have excitatory synaptic action at some of its axon terminals and inhibitory action at others. The answer is no. Two different kinds of nerve cells are needed, one for each type of transmission and synaptic transmitter substance. This can readily be demonstrated by the effect of strychnine and tetanus toxins in the spinal cord; They specifically prevent inhibitory synaptic action and leave excitatory action unaltered. As a result the synaptic excitation of nerve cells is uncontrolled and convulsions result. The special types of cells responsible for inhibitory synaptic action are now being recognized in many parts of the central nervous system.
This account of communication between nerve cells is necessarily oversimplified, yet it shows that some significant advances are being made at the level of individual components of the nervous system. By selecting the most favorable situations we have been able to throw light on some details of nerve-cell behavior. We can be encouraged by these limited successes. But the task of understanding in a comprehensive way how the human brain operates staggers its own imagination.
Our brain begins with its portion of the central nervous system contained within the skull. The brain is the control center for movement, sleep, hunger, thirst, and virtually every other vital activity necessary to survival. All human emotions - including love, hate, fear, anger, elation, and sadness - are controlled by the brain. It also receives and interprets the countless signals that are sent to it from other parts of the body and from the external environment. The brain makes us conscious, emotional, and intelligent
Human Brain
The human brain has three major structural components: the large dome-shaped cerebrum , the smaller somewhat spherical cerebellum, and the brainstem. Prominent in the brainstem are the medulla oblongata and the thalamus - between the medulla and the cerebrum. The cerebrum is responsible for intelligence and reasoning. The cerebellum helps to maintain balance and posture. The medulla is involved in maintaining involuntary functions such as respiration, and the thalamus act as a relay center for electrical impulses traveling to and from the cerebral cortex.
The adult human brain is a 1.3-kg. (3-lb.) Mass of pinkish-gray jellylike tissue made up of approximately 100 billion nerve cells or neurons: The Neuroglia (supporting-tissue) cells, and vascular (blood-carrying) and other tissues.
Between the brain and the cranium - the part of the skull that directly covers the brain - are three protective membranes, or meninges. The outermost membrane, the dura mater, is the toughest and thickest. Below the dura mater is a middle membrane, called the arachnoid layer. The innermost membrane, the pia mater, consists mainly of small blood vessels and follows the contours of the surface of the brain.
A clear liquid, the cerebrospinal fluid, bathes the entire brain and fills a series of four cavities, called ventricles, near the center of the brain. The cerebrospinal fluid protects the internal portion of the brain from varying pressures and transports chemical substances within the nervous system.
From the outside, the brain appears as three associatively distinct but connected parts, the cerebrum (the Latin word for brain) - two large, almost symmetrical hemispheres; the cerebellum ('little brain') - two smaller hemispheres located at the back of the cerebrum; and the brain stem - a central core that gradually becomes the spinal cord, exiting the skull through an opening at its base called the foramen magnum. Two other major parts of the brain, the thalamus and the hypothalamus, lie in the midline above the brain stem underneath the cerebellum.
The brain and the spinal cord together make up the central nervous system, which communicates with the rest of the body through the peripheral nervous system. The peripheral nervous system consists of 12 pairs of cranial nerves extending from the cerebrum and brain stem; a system of other nerves branching throughout the body from the spinal cord, and the autonomic nervous system, which regulates vital functions not under conscious control, such as the activity of the heart muscle, smooth muscle (involuntary muscle found in the skin, blood vessels, and internal organs), and glands.
Many motor and sensory functions have been “mapped” to specific areas of the cerebral cortex, some of which are indicated here. In general, these areas exist in both hemispheres of the cerebrum, each serving the opposite side of the body. Fewer defined are the areas of association, located mainly in the frontal cortex, operatives in functions of thought and emotion and responsible for linking input from different senses. The areas of language are an exception: Both Wernicke’s area, concerned with the comprehension of spoken language, and Broca’s area, governing the production of speech, have been pinpointed on the cortex.
Most high-level brain functions take place in the cerebrum. Its two large hemispheres make up approximately 85 percent of the brain's weight. The exterior surface of the cerebrum, the cerebral cortex, is a convoluted, or folded, grayish layer of cell bodies known as the gray matter. The gray matter covers an underlying mass of fibers called the white matter. The convolutions are made up of ridgelike bulges, known as gyri, separated by small grooves called sulci and larger grooves called fissures. Approximately two-thirds of the cortical surface is hidden in the folds of the sulci. The extensive convolutions enable a very large surface area of brain cortex - roughly, 1.5 m2 (16 ft2) in an adult - to fit within the cranium. The pattern of these convolutions is similar, although not identical, in all humans.
The two cerebral hemispheres are partially separated from each other by a deep fold known as the longitudinal fissure. Communication between the two hemispheres is through several concentrated bundles of axons, called commissures, the largest of which is the corpus callosum.
Several major sulci divides the cortex into distinguishable regions. The central sulcus, or Rolandic fissure, runs from the middle of the top of each hemisphere downward, forwards, and toward another major sulcus, the lateral (side), or Sylvian, sulcus. These and other sulci and gyri divide the cerebrum into five lobes: The frontal, parietal, temporal, and occipital lobes and the insula.
Although the cerebrum is symmetrical in structure, with two lobes emerging from the brain stem and matching motor and sensory areas in each, certain intellectual functions are restricted to one hemisphere. A person’s dominant hemisphere is usually occupied with language and logical operations, while the other hemisphere controls emotion and artistic and spatial skills. In nearly all right-handed and many left-handed people, the left hemisphere is dominant.
The frontal lobe is the largest of the five and consists of all the cortices in front of the central sulcus. Broca's area, a part of the cortex related to speech, is located in the frontal lobe. The parietal lobe consists of the cortex behind the central sulcus to a sulcus near the back of the cerebrum known as the parieto-occipital sulcus. The parieto-occipital sulcus, in turn, forms the front border of the occipital lobe, which are the rearmost part of the cerebrum. The temporal lobe is to the side of and below the lateral sulcus. Wernicke's area, a part of the cortex related to the understanding of language, is located in the temporal lobe. The insula lies deep within the folds of the lateral sulcus.
The cerebrum receives information from all the sense organs and sends motor commands (signals that results in activity in the muscles or glands) to other parts of the brain and the rest of the body. Motor commands are transmitted by the motor cortex, a strip of cerebral cortex extending from side to side across the top of the cerebrum just in front of the central sulcus. The sensory cortex, parallel strips of cerebral cortex just in back of the central sulcus, receives input from the sense organs.
Many other areas of the cerebral cortex have also been mapped according to their specific functions, such as vision, hearing, speech, emotions, language, and other aspects of perceiving, thinking, and remembering. Cortical regions known as associative cortices are responsible for integrating multiple inputs, processing the information, and carrying out complex responses.
The cerebellum coordinates body movements. Located at the lower back of the brain beneath the occipital lobes, the cerebellum is divided into two lateral (side-by-side) lobes connected by a fingerlike bundle of white fibers called the vermis. The outer layer, or cortex, of the cerebellum consists of fine folds called folia. As in the cerebrum, the outer layer of cortical gray matter surrounds a deeper layer of white matter and nuclei (groups of nerve cells). Three fiber bundles called cerebellar peduncles connect the cerebellum to the three parts of the brain stem - the midbrain, the pons, and the medulla oblongata.
The cerebellum coordinates voluntary movements by fine-tuning commands from the motor cortex in the cerebrum. The cerebellum also maintains posture and balance by controlling muscle tone and sensing the position of the limbs. All motor activity, from hitting a baseball to fingering a violin, depends on the cerebellum.
The limbic system is a group of brain structures that play a role in emotion, memory, and motivation. For example, electrical stimulation of the amygdala in laboratory animals can provoke fear, anger, and aggression. The hypothalamus regulates hunger, thirst, sleep, body temperature, sexual drive, and other functions.
The thalamus and the hypothalamus lie underneath the cerebrum and connect it to the brain stem. The thalamus consist of two rounded masses of gray tissue lying within the middle of the brain, between the two cerebral hemispheres. The thalamus is the main relay station for incoming sensory signals to the cerebral cortex and for outgoing motor signals from it. All sensory input to the brain, except that of the sense of smell, connects to individual nuclei of the thalamus.
The hypothalamus lies beneath the thalamus on the midline at the base of the brain. It regulates or is involved directly in the control of many of the body's vital drives and activities, such as eating, drinking, temperature regulation, sleep, emotional behavior, and sexual activity. It also controls the function of internal body organs by means of the autonomic nervous system, interacts closely with the pituitary gland, and helps coordinate activities of the brain stem.
The brain stem, shown here in colored cross section, is the lowest part of the brain. It serves as the path for messages traveling between the upper brain and spinal cord but is also the seat of basic and vital functions such as breathing, blood pressure, and heart rates, as well as reflexes like eye movement and vomiting. The brain stem has three main parts: the medulla, pons, and midbrain. A canal runs longitudinally through these structures carrying cerebrospinal fluid. Also distributed along its length is a network of cells, referred to as the reticular formation, that governs the state of alertness.
The brain stem is revolutionarily the most primitive part of the brain and is responsible for sustaining the basic functions of life, such as breathing and blood pressure. It includes three main structures lying between and below the two cerebral hemispheres - the midbrain, pons, and medulla oblongata.
The topmost structure of the brain stem is the midbrain. It contains major relay stations for neurons transmitting signals to the cerebral cortex, as well as many reflex centers - pathways carrying sensory (input) information and motor (output) command. Relays and reflex centers for visual and auditory (hearing) functions are located in the top portion of the midbrain. A pair of nuclei called the superior colliculus control reflex actions of the eye, such as blinking, opening and closing the pupil, and focusing the lens. A second pair of nuclei, called the inferior colliculus, controls auditory reflexes, such as adjusting the ear to the volume of sound. At the bottom of the midbrain are reflex and relay centers relating to pain, temperature, and touch, as well as several regions associated with the control of movement, such as the red nucleus and the substantia nigra.
Continuous with and below the midbrain and directly in front of the cerebellum is a prominent bulge in the brain stem called the pons. The pons consists of large bundles of nerve fibers that connect the two halves of the cerebellum and also connect each side of the cerebellum with the opposite-side cerebral hemisphere. The pons serves mainly as a relay station linking the cerebral cortex and the medulla oblongata.
The long, stalklike lowermost portion of the brain stem is called the medulla oblongata. At the top, it is continuous with the pons and the midbrain; at the bottom, it makes a gradual transition into the spinal cord at the foramen magnum. Sensory and motor nerve fibers connecting the brain and the rest of the body cross over to the opposite side as they pass through the medulla. Thus, the left half of the brain communicates with the right half of the body, and the right half of the brain with the left half of the body.
Running up the brain stem from the medulla oblongata through the pons and the midbrain is a netlike formation of nuclei known as the reticular formation. The reticular formation controls respiration, cardiovascular function, digestion, levels of alertness, and patterns of sleep. It also determines which parts of the constant flow of sensory information into the body are received by the cerebrum.
There are two main types of brain cells, neurons and neuroglia. Neurons are responsible for the transmission and analysis of all electrochemical communication within the brain and other parts of the nervous system. Each neuron is composed of a cell body called a soma, a major fiber called an axon, and a system of branches called dendrites. Axons, also called nerve fibers, convey electrical signals away from the soma and can be up to 1 m. (3.3 ft.) in length. Most axons are covered with a protective sheath of myelin, a substance made of fats and protein, which insulates the axon. Myelinated axons conduct neuronal signals faster than do unmyelinated axons. Dendrites convey electrical signals toward the soma, are shorter than axons, and are usually multiple and branching.
Neuroglial cells are twice as numerous as neurons and account for half of the brain's weight. Neuroglia (from glia, Greek for 'glue') provide structural support to the neurons. Neuroglial cells also form myelin, guide developing neurons, take up chemicals involved in cell-to-cell communication, and contribute to the maintenance of the environment around neurons.
Twelve pairs of cranial nerves arise symmetrically from the base of the brain and are numbered, from front to back, in the order in which they arise. They connect mainly with structures of the head and neck, such as the eyes, ears, nose, mouth, tongue, and throat. Some are motor nerves, controlling muscle movement; some are sensory nerves, conveying information from the sense organs; and others contain fibers for both sensory and motor impulses. The first and second pairs of cranial nerves - the olfactory (smell) nerves and the optic (vision) nerve - carry sensory information from the nose and eyes, respectively, to the undersurface of the cerebral hemispheres. The other ten pairs of cranial nerves originate in or end in the brain stem.
The brain functions by complex neuronal, or nerve cell, circuits. Communication between neurons is both electrical and chemical and always travels from the dendrites of a neuron, through its soma, and out its axon to the dendrites of another neuron.
Dendrites of one neuron receive signals from the axons of other neurons through chemicals known as neurotransmitters. The neurotransmitters set off electrical charges in the dendrites, which then carry the signals electrochemically to the soma. The soma integrates the information, which is then transmitted electrochemically down the axon to its tip.
At the tip of the axon, small, bubble-like structures called vesicle’s release neurotransmitters that carry the signal across the synapse, or gap, between two neurons. There are many types of neurotransmitters, including norepinephrine, dopamine, and serotonin. Neurotransmitters can be excitatory (that is, they excite an electrochemical response in the dendrite receptors) or inhibitory (they block the response of the dendrite receptors).
One neuron may communicate with thousands of other neurons, and many thousands of neurons are involved with even the simplest behavior. It is believed that these connections and their efficiency can be modified, or altered, by experience.
Scientists have used two primary approaches to studying how the brain works. One approach is to study brain function after parts of the brain have been damaged. Functions that disappear or that is no longer normal after injury to specific regions of the brain can often be associated with the damaged areas. The second approach is to study the response of the brain to direct stimulation or to stimulation of various sense organs.
Neurons are grouped by function into collections of cells called nuclei. These nuclei are connected to form sensory, motor, and other systems. Scientists can study the function of somatosensory (pain and touch), motor, olfactory, visual, auditory, language, and other systems by measuring the physiological (physical and chemical) changes that occur in the brain when these senses are activated. For example, electroencephalography (EEG) measures the electrical activity of specific groups of neurons through electrodes attached to the surface of the skull. Electrodes incorporate directly into the brain can give readings of individual neurons. Changes in blood flow, glucose (sugar), or oxygen consumption in groups of active cells can also be mapped.
Although the brain appears symmetrical, how it functions is not. Each hemisphere is specializing and dominates the other in certain functions. Research has shown that hemispheric dominance is related to whether a person is predominantly right-handed or left-handed. In most right-handed people, the left hemisphere processes arithmetic, language, and speech. The right hemisphere interprets music, complex imagery, and spatial relationships and recognizes and expresses emotion. In left-handed people, the pattern of brain organization is more variable.
Hemispheric specialization has traditionally been studied in people who have sustained damage to the connections between the two hemispheres, as may occur with a stroke, an interruption of blood flow to an area of the brain that causes the death of nerve cells in that area. The division of functions between the two hemispheres has also been studied in people who have had to have the connection between the two hemispheres surgically cut in order to control severe epilepsy, a neurological disease characterized by convulsions and loss of consciousness.
The visual system of humans is one of the most advanced sensory systems in the body. More information is conveyed visually than by any other means. In addition to the structures of the eye itself, several cortical regions - collectively called a primary visual and visual associative cortex - as well as the midbrain are involved in the visual system. Conscious processing of visual input occurs in the primary visual cortex, but reflexive - that is, immediate and unconscious - responses occur at the superior colliculus in the midbrain. Associative cortical regions - specialized regions that can associate, or integrate, multiple inputs - in the parietal and frontal lobes along with parts of the temporal lobe are also involved in the processing of visual information and the establishment of visual memories.
Language involves specialized cortical regions in a complex interaction that allows the brain to comprehend and communicate abstract ideas. The motor cortex initiates impulses that travel through the brain stem to produce audible sounds. Neighboring regions of motor cortices, called the supplemental motor cortex, are involved in sequencing and coordinating sounds. Broca's area of the frontal lobe is responsible for the sequencing of language elements for output. The comprehension of language is dependent upon Wernicke's area of the temporal lobe. Other cortical circuits connect these areas.
Memory is usually considered a diffusely stored associative process - that is, it puts together information from many different sources. Although research has failed to identify specific sites in the brain as locations of individual memories, certain brain areas are critical for memory to function. Immediate recall - the ability to repeat short series of words or numbers immediately after hearing them - is thought to be located in the auditory associative cortex. Short-term memory - the ability to retain a limited amount of information for up to an hour - is located in the deep temporal lobe. Long-term memory probably involves exchanges between the medial temporal lobe, various cortical regions, and the midbrain.
The autonomic nervous system regulates the life support systems of the body reflexively - that is, without conscious direction. It automatically controls the muscles of the heart, digestive system, and lungs; Certain glands, and homeostasis - that is, the equilibrium of the internal environment of the body. The autonomic nervous system itself is controlled by nerve centers in the spinal cord and brain stem and is fine-tuned by regions higher in the brain, such as the midbrain and cortex. Reactions such as blushing indicate that cognitive, or thinking, centers of the brain are also involved in autonomic responses.
The brain is guarded by several highly developed protective mechanisms. The bony cranium, the surrounding meninges, and the cerebrospinal fluid all contribute to the mechanical protection of the brain. In addition, a filtration system called the blood-brain barrier protects the brain from exposure to potentially harmful substances carried in the bloodstream.
Brain disorders have a wide range of causes, including head injury, stroke, bacterial diseases, complex chemical imbalances, and changes associated with aging.
Head injury can initiate a cascade of damaging events. After a blow to the head, a person may be stunned or may become unconscious for a moment. This injury, called - concussion, - usually leaves no permanent damage. If the blow is more severe and hemorrhage (excessive bleeding) and swelling occurs, however, severe headache, dizziness, paralysis, a convulsion, or temporary blindness may result, depending on the area of the brain affected. Damage to the cerebrum can also result in profound personality changes.
Damage to Broca's area in the frontal lobe causes difficulty in speaking and writing, a problem known as Broca's aphasia. Injury to Wernicke's area in the left temporal lobe results in an inability to comprehend spoken language, called Wernicke's aphasia.
An injury or disturbance to a part of the hypothalamus may cause a variety of different symptoms, such as loss of appetite with an extreme drop in body weight, increase in appetite leading to obesity; Extraordinary thirst with excessive urination (diabetes insipidus), failure in body-temperature control, resulting in either low temperature (hypothermia) or high temperature (fever), excessive emotionality, and uncontrolled anger or aggression. If the relationship between the hypothalamus and the pituitary gland is damaged, other vital bodily functions may be disturbed, such as sexual function, metabolism, and cardiovascular activity.
Injury to the brain stem is even more serious because it houses the nerve centers that control breathing and heart action. Damage to the medulla oblongata usually results in immediate death.
A stroke is damage to the brain due to an interruption in blood flow. The interruption may be caused by a blood clot, constriction of a blood vessel, or rupture of a vessel accompanied by bleeding. A pouchlike expansion of the wall of a blood vessel, called an aneurysm, may weaken and burst, for example, because of high blood pressure.
Sufficient quantities of glucose and oxygen, transported through the bloodstream, are needed to keep nerve cells alive. When the blood supply to a small part of the brain is interrupted, the cells in that area die and the function of the area is lost. A massive stroke can cause a one-sided paralysis (hemiplegia) and sensory loss on the side of the body opposite the hemisphere damaged by the stroke.
Some brain diseases, such as multiple sclerosis and Parkinson disease, are progressive, becoming worse over time. Multiple sclerosis damages the myelin sheath around axons in the brain and spinal cord. As a result, the affected axons cannot transmit nerve impulses properly. Parkinson disease destroys the cells of the substantia nigra in the midbrain, resulting in a deficiency in the neurotransmitter dopamine that affects motor functions.
Cerebral palsy is a broad term for brain damage sustained close to birth that permanently affects motor function. The damage may take place either in the developing fetus, during birth, or just after birth and is the result of the faulty development or breaking down of motor pathways. Cerebral palsy is nonprogressive - that is, it does not worsen with time.
A bacterial infection in the cerebrum or in the coverings of the brain, swelling of the brain, or an abnormal growth of healthy brain tissue can all cause an increase in intracranial pressure and result in serious damage to the brain.
Scientists are finding that certain brain chemical imbalances are associated with mental disorders such as schizophrenia and depression. Such findings have changed scientific understanding of mental health and have resulted in new treatments that chemically correct these imbalances.
During childhood development, the brain is particularly susceptible to damage because of the rapid growth and reorganization of nerve connections. Problems that originate in the immature brain can appear as epilepsy or other brain-function problems in adulthood.
Several neurological problems are common in aging. Alzheimer's disease damages many areas of the brain, including the frontal, temporal, and parietal lobes. The brain tissue of people with Alzheimer's disease shows characteristic patterns of damaged neurons, known as plaques and tangles. Alzheimer's disease produces progressive dementia, characterized by symptoms such as failing attention and memory, loss of mathematical ability, irritability, and poor orientation in space and time.
A magnetic resonance imaging (MRI) scan of the human brain reveals the contours of one of the brain’s hemispheres. The gyri, or ridges, appear in red, while the sulci, or valleys, are shown in blue. Each person has slightly different patterns of gyri and sulci, which reflect individual differences in brain development.
Several commonly used diagnostic methods give images of the brain without invading the skull. Some portray anatomy - that is, the structure of the brain - whereas others measure brain function. Two or more methods may be used to complement each other, together providing a more complete picture than would be possible by one method alone.
Magnetic resonance imaging (MRI), introduced in the early 1980s, beams high-frequency radio waves into the brain in a highly magnetized field that causes the protons that form the nuclei of hydrogen atoms in the brain to reemit the radio waves. The reemitted radio waves are analyzed by computer to create thin cross-sectional images of the brain. MRI provides the most detailed images of the brain and is safer than imaging methods that use X-rays. However, MRI is a lengthy process and also cannot be used with people who have pacemakers or metal implants, both of which are adversely affected by the magnetic field.
Computed tomography (CT), also known as CT scans, developed in the early 1970s. This imaging method X-rays the brain from many different angles, feeding the information into a computer that produces a series of cross-sectional images. CT is particularly useful for diagnosing blood clots and brain tumors. It is a much quicker process than magnetic resonance imaging and is therefore advantageous in certain situations - for example, with people who are extremely ill.
This positron emission tomography (PET) scans of the brain shows the activity of brain cells in the resting state and during three types of auditory stimulation. PET uses radioactive substances introduced within the brain to measure such brain functions as cerebral metabolism, blood flow and volume, oxygen use, and the formation of neurotransmitters. This imaging method collects data from many different angles, feeding the information into a computer that produces a series of cross-sectional images.
Changes in brain function due to brain disorders can be visualized in several ways. Magnetic resonance spectroscopy measures the concentration of specific chemical compounds in the brain that may change during specific behaviors. Functional magnetic resonance imaging (fMRI) maps changes in oxygen concentration that correspond to nerve cell activity.
Positron emission tomography (PET), developed in the mid-1970s, uses computed tomography to visualize radioactive tracers, radioactive substances are introduced into the brain intravenously or by inhalation. PET can measure such brain functions as cerebral metabolism, blood flow and volume, oxygen use, and the formation of neurotransmitters. Single photon emission computed tomography (SPECT), developed in the 1950s and 1960s, uses radioactive tracers to visualize the circulation and volume of blood in the brain.
Brain-imaging studies have provided new insights into sensory, motor, language, and memory processes, as well as brain disorders such as epilepsy, cerebrovascular disease; Alzheimer's, Parkinson, and Huntington's diseases, and various mental disorders, such as schizophrenia.
Evolution of the Brain
Although all vertebrate brains share the same basic three-part structure, the development of their constituent parts varies across the evolutionary scale. In fish, the cerebrum is dwarfed by the rest of the brain and serves mostly to process input from the senses. In reptiles and amphibians, the cerebrum is proportionally larger and begins to connect and form conclusions about this input. Birds have well-developed optic lobes, making the cerebrum even larger. Among mammals, the cerebrum dominates the brain. It is most developed among primates, in whom cognitive ability is the highest.
In lower vertebrates, such as fish and reptiles, the brain is often tubular and bears a striking resemblance to the early embryonic stages of the brains of more highly evolved animals. In all vertebrates, the brain is divided into three regions: the forebrain (prosencephalon), the midbrain (mesencephalon), and the hindbrain (rhombencephalon). These three regions further sub-divide into different structures, systems, nuclei, and layers.
The more highly evolved the animal, the more complex is the brain structure. Human beings have the most complex brains of all animals. Evolutionary forces have also resulted in a progressive increase in the size of the brain. In vertebrates lower than mammals, the brain is small. In meat-eating animals, particularly primates, the brain increases dramatically in size.
The cerebrum and cerebellum of higher mammals are highly convoluted in order to fit the most gray matter surface within the confines of the cranium. Such highly convoluted brains are called gyrencephalic. Many lower mammals have a smooth, or lissencephalic (smooth head), cortical surfaces.
There is also evidence of evolutionary adaption of the brain. For example, many birds depend on an advanced visual system to identify food at great distances while in flight. Consequently, their optic lobes and cerebellum are well developed, giving them keen sight and outstanding motor coordination in flight. Rodents, on the other hand, as nocturnal animals, do not have a well-developed visual system. Instead, they rely more heavily on other sensory systems, such as a highly-developed sense of smell and facial whiskers.
Recent research in brain function suggests that there may be sexual differences in both brain anatomy and brain function. One study indicated that men and women may use their brains differently while thinking. Researchers used functional magnetic resonance imaging to observe which parts of the brain were activated as groups of men and women tried to determine whether sets of nonsense words rhymed. Men used only Broca's area in this task, whereas women used Broca's area plus an area on the right side of the brain.
THE CELL
The Cell, in [biology] is the most basic unit of life. Cells are the smallest structures capable of basic life processes, such as taking in nutrients, expelling waste, and reproducing. All living things are composed of cells. Some microscopic organisms, such as bacteria and protozoa, are unicellular, meaning they consist of a single cell. Plants, animals, and fungi are multicellular; that is, they are composed of a great many cells working in concert. But whether it makes up an entire bacterium or is just one of the trillions in a human being, the cell is a marvel of design and efficiency. Cells carry out thousands of biochemical reactions each minute and reproduce new cells that perpetuate life.
The word cell refers to several types of organisms. Cells such as paramecia, dinoflagellates, diatoms, and spirochetes are self-maintaining organisms; cells such as lymphocytes, erythrocytes, muscle cells, nerve cells, cardiac muscle, and chromoplasts are more specialized cells that are a part of higher multicellular organisms. Nonetheless, of its size or whether the cell is a complete organism or just part of an organism, all cells have certain structural components in common. All cells have some type of outer cell boundary that permits some materials to leave and enter the cell and a cell interior composed of a water-rich, fluid material called cytoplasm that contains hereditary material in the form of deoxyribonucleic acid (DNA).
Cells vary considerably in size. The smallest cell, a type of bacterium known as a mycoplasma, measures 0.0001 mm. (0.000004 in.) in diameter; 10,000 mycoplasmas in a row are only as wide as the diameter of a human hair. Among the largest cells are the nerve cells that run down a giraffe’s neck; these cells can exceed 3 m. (9.7 ft.) in length. Human cells also display a variety of sizes, from small red blood cells that measure 0.00076 mm. (0.00003 in.) to liver cells that may be ten times larger. About 10,000 average-sized human cells can fit on the head of a pin.
Along with their differences in size, cells present an array of shapes. Some, such as the bacterium Escherichia coli, resemble rods. The paramecium, a type of protozoan, is a slipper shaped; and the amoeba, another protozoan, has an irregular form that changes shape as it moves around. Plant cells typically resemble boxes or cubes. In humans, the outermost layers of skin cells are flat, while muscle cells are long and thin. Some nerve cells, with their elongated, tentacle-like extensions, suggest an octopus.
In multicellular organisms, shape is typically tailored to the cell’s job. For example, flat skin cells pack tightly into a layer that protects the underlying tissues from invasions by bacteria. Long, thin muscle cells’ contract readily to move bones. The numerous extensions from a nerve cell enable it to connect to several other nerve cells in order to send and receive messages rapidly and efficiently.
By itself, each cell is a model of independence and self-containment. Like some miniature, walled city in perpetual rush hour, the cell constantly bustles with traffic, shuttling essential molecules from place to place to carry out the business of living. Despite their individuality, however, cells also display a remarkable ability to join, communicate, and coordinate with other cells. The human body, for example, consists of an estimated 20 to 30 trillion cells. Dozens of different kinds of cells are organized into specialized groups called tissues. Tendons and bones, for example, are composed of connective tissue, whereas skin and mucous membranes are built from epithelial tissue. Different tissue types are assembled into organs, which are structures specialized to perform particular functions. Examples of organs include the heart, stomach, and brain. Organs, in turn, are organized into systems such as the circulatory, digestive, or nervous systems. All together, these assembled organ systems form the human body.
The components of cells are molecules, nonliving structures formed by the union of atoms. Small molecules serve as building blocks for larger molecules. Proteins, nucleic acids, carbohydrates, and lipids, which include fats and oils, are the four major molecules that underlie cell structure and also participate in cell functions. For example, a tightly organized arrangement of lipids, proteins, and protein-sugar compounds forms the plasma membrane, or outer boundary, of certain cells. The organelles, membrane-bound compartments in cells, are built largely from proteins. Biochemical reactions in cells are guided by enzymes, specialized proteins that speed up chemical reactions. The nucleic acid deoxyribonucleic acid (DNA) contains the hereditary information for cells, and another nucleic acid, ribonucleic acid (RNA), works with DNA to build the thousands of proteins the cell needs.
Cells fall into one of two categories: Prokaryotic or eukaryotic, in a prokaryotic cell, found only in bacteria and archaebacteria, all the components, including the DNA, mingle freely in the cell’s interior, a single compartment. Eukaryotic cells, which make up plants, animals, fungi, and all other life forms, contain numerous compartments, or organelles, within each cell. The DNA in eukaryotic cells is enclosed in a special organelle called the nucleus, which serves as the cell’s command center and information library. The term prokaryote comes from Greek words that mean “before the nucleus” or “prenucleus,” while eukaryote means “true nucleus.”
Bacteria’s cells typically are surrounded by a rigid, protective cell wall. The cell membrane, also called the plasma membrane, regulates passage of materials into and out of the cytoplasm, the semi-fluid that fill the cell. The DNA, located in the nucleoid region, contains the genetic information for the cell. Ribosomes carry out protein synthesis. Many bacteria contain a pilus (plural pili), a structure that extends out of the cell to transfer DNA to another bacterium. The flagellum, found in numerous species, is used for the locomotion. Some bacteria contain a plasmid, a small chromosomes with extra genes. Others have a capsule, a sticky substance external to the cell wall that protects bacteria from attack by white blood cells. Mesosomes were formerly thought to be structures with unknown functions, but now are known to be artifacts created when cells are prepared for viewing with electron microscopes.
Prokaryotic cells are among the tiniest of all cells, ranging in size from 0.0001 to 0.003 mm. (0.000004 to 0.0001 in.) in diameter. About a hundred typical prokaryotic cells lined up in a row would match the thickness of a book page. These cells, which can be rod-like, spherical, or spiral in shape, are surrounded by a protective cell wall. Like most cells, prokaryotic cells live in a watery environment, whether it is soil moisture, a pond, or the fluid surrounding cells in the human body. Tiny pores in the cell wall enable water and the substances dissolved in it, such as oxygen, to flow into the cell; these pores also allow wastes to flow out.
Pushed up against the inner surface of the prokaryotic cell wall is a thin membrane called the plasma membrane. The plasma membrane, composed of two layers of flexible lipid molecules and interspersed with durable proteins, is both supple and strong. Unlike the cell wall, whose open pores allow the unregulated traffic of materials in and out of the cell, the plasma membrane is selectively permeable, meaning it allows only certain substances to pass through. Thus, the plasma membrane actively separates the cell’s contents from its surrounding fluids.
While small molecules such as water, oxygen, and carbon dioxide diffuse freely across the plasma membrane, the passage of many larger molecules, including amino acids (the building blocks’ of proteins) and sugars, is carefully regulated. Specialized transport proteins accomplish this task. The transport proteins span the plasma membrane, forming an intricate system of pumps and channels through which traffic is conducted. Some substances swirling in the fluid around the cell can enter it only if they bind to and are escorted in by specific transport proteins. In this way, the cell fine-tunes its internal environment.
The plasma membrane encloses the cytoplasm, the semifluid that fill the cell. Composed of about 65 percent water, the cytoplasm is packed with up to a billion molecules per cell, a rich storehouse that includes enzymes and dissolved nutrients, such as sugars and amino acids. The water provides a favorable environment for the thousands of biochemical reactions that take place in the cell.
Within the cytoplasm of all prokaryote is deoxyribonucleic acid (DNA), a complex molecule in the form of a double helix, a shape similar to a spiral staircase. The DNA is about 1,000 times the length of the cell, and to fit inside, it repeatedly twists and folds to form a compact structure called a chromosome. The chromosome in prokaryote is circular, and is located in a region of the cell called the nucleoid. Often, smaller chromosomes called plasmids are located in the cytoplasm. The DNA is divided into units called genes, just like a long train is divided into separate cars. Depending on the species, the DNA contains several hundred or even thousands of genes. Typically, one gene contains coded instructions for building all or part of a single protein. Enzymes, which are specialized proteins, determine virtually all the biochemical reactions that support and sustain the cell.
Also immersed in the cytoplasm are the only organelles in prokaryotic cells - tiny bead-like structures called ribosomes. These are the cell’s protein factories. Following the instructions encoded in the DNA, ribosomes churn out proteins by the hundreds every minute, providing needed enzymes, the replacements for worn-out transport proteins, or other proteins required by the cell.
While relatively simple in construction, prokaryotic cells display extremely complex activity. They have a greater range of biochemical reactions than those found in their larger relatives, the eukaryotic cells. The extraordinary biochemical diversity of prokaryotic cells is manifested in the wide-ranging lifestyles of the archaebacteria and the bacteria, whose habitats include polar ice, deserts, and hydrothermal vents - deep regions of the ocean under great pressure where hot water geysers erupt from cracks in the ocean floor.
An animal cell typically contains several types of membrane-bound organs, or organelles. The nucleus directs activities of the cell and carries genetic information from generation to generation. The mitochondria generate energy for the cell. Proteins are manufactured by ribosomes, which are bound to the rough endoplasmic reticulum or float free in the cytoplasm. The Golgi apparatus modifies, packages, and distributes proteins while lysosomes store enzymes for digesting food. The entire cell is wrapped in a lipid membrane that selectively permits materials to pass in and out of the cytoplasm.
Eukaryotic cells are typically about ten times larger than prokaryotic cells. In animal cells, the plasma membrane, rather than a cell wall, forms the cell’s outer boundary. With a design similar to the plasma membrane of prokaryotic cells, it separates the cell from its surroundings and regulates the traffic across the membrane.
The eukaryotic cell cytoplasm is similar to that of the prokaryote cell except for one major difference: Eukaryotic cells house a nucleus and numerous other membrane-enclosed organelles. Like separate rooms of a house, these organelles enable specialized functions to be carried out efficiently. The building of proteins and lipids, for example, takes place in separate organelles where specialized enzymes geared for each job are located.
The plasma membrane that surrounds eukaryotic cells is a dynamic structure composed of two layers of phospholipid molecules interspersed with cholesterol and proteins. Phospholipids are composed of a hydrophilic, or water-loving, head and two tails, which are hydrophobic, or water-hating. The two phospholipid layers face each other in the membrane, with the heads directed outward and the tails pointing inward. The water-attracting heads anchor the membrane to the cytoplasm, the watery fluid inside the cell, and also to the water surrounding the cell. The water-hating tails block large water-soluble molecules from passing through the membrane while permitting fat-soluble molecules, including medications such as tranquilizers and sleeping pills, to freely cross the membrane. Proteins embedded in the plasma membrane carry out a variety of functions, including transport of large water soluble molecules such as sugars and certain amino acids. Glycoproteins, proteins bonded to carbohydrates, serve in part to identify the cell as belonging to a unique organism, enabling the immune system to detect foreign cells, such as invading bacteria, which carry different glycoproteins. Cholesterol molecules in the plasma membrane act as stabilizers that limit the movement of the two slippery phospholipids layer, which slide back and forth in the membrane. Tiny gaps in the membrane enable small molecules such as oxygen to diffuse readily into and out of the cell. Since cells constantly use up oxygen, decreasing its concentration within the cell, the higher concentration of oxygen outside the cell causes a net flow of oxygen into the cell. The steady stream of oxygen into the cell enables it to carry out aerobic respiration continually, a process that provides the cell with the energy needed to carry out its functions.
The nucleus is the largest organelle in an animal cell. It contains numerous strands of DNA, the length of each strand being many times the diameter of the cell. Unlike the circular prokaryotic DNA, long sectors of eukaryotic DNA pack into the nucleus by wrapping around proteins. As a cell begins to divide, each DNA strand folds over onto itself several times, forming a rod-shaped chromosome.
The nucleus is surrounded by a double-layered membrane that protects the DNA from potentially damaging chemical reactions that occur in the cytoplasm. Messages pass between the cytoplasm and the nucleus through nuclear pores, which are holes in the membrane of the nucleus. In each nuclear pore, molecular signals flash back and forth as often as ten times per second. For example, a signal to activate a specific gene comes into the nucleus and instructions for production of the necessary protein go out to the cytoplasm.
The nucleus, present in eukaryotic cells, is a discrete structure containing chromosomes, which hold the genetic information for the cell. Separated from the cytoplasm of the cell by a double-layered membrane called the nuclear envelope, the nucleus contains a cellular material called nucleoplasm. Nuclear pores, present around the circumference of the nuclear membrane, allow the exchange of cellular materials between the nucleoplasm and the cytoplasm.
Attached to the nuclear membrane is an elongated membranous sac called the endoplasmic reticulum. This organelle tunnels through the cytoplasm, folding back and forth on itself to form a series of membranous stacks. Endoplasmic reticulums take two forms: Rough and smooth. A rough endoplasmic reticulum (RER) is so called because it appears bumpy under a microscope. The bumps are actually thousands of ribosomes attached to the membrane’s surface. The ribosomes in eukaryotic cells have the same function as those in prokaryotic cells - protein synthesis - but they differ slightly in structure. Eukaryote ribosomes bound to the endoplasmic reticulum help assemble proteins that typically are exported from the cell. The ribosomes work with other molecules to link amino acids to partially completed proteins. These incomplete proteins then travel to the inner chamber of the endoplasmic reticulum, where chemical modifications, such as the addition of a sugar, are carried out. Chemical modifications of lipids are also carried out in the endoplasmic reticulum.
The endoplasmic reticulum and its bound ribosomes are particularly dense in cells that produce many proteins for export, such as the white blood cells of the immune system, which produce and secrete antibodies. Some ribosomes that manufacture proteins are not attached to the endoplasmic reticulum. These so-called free ribosomes are dispersed in the cytoplasm and typically make proteins - many of them enzymes - that remain in the cell.
The second form of endoplasmic reticulum, the smooth endoplasmic reticulum (SER), lacks ribosomes and has an even surface. Within the winding channels of the smooth endoplasmic reticulum are the enzymes needed for the construction of molecules such as carbohydrates and lipids. The smooth endoplasmic reticulum is prominent in liver cells, where it also serves to detoxify substances such as alcohol, drugs, and other poisons.
Proteins are transported from free and bound ribosomes to the Golgi apparatus, an organelle that resembles a stack of deflated balloons. It is packed with enzymes that complete the processing of proteins. These enzymes add sulfur or phosphorus atoms to certain regions of the protein, for example, or chop off tiny pieces from the ends of the proteins. The completed protein then leaves the Golgi apparatus for its final destination inside or outside the cell. During its assembly on the ribosome, each protein has acquired a group of from 4 to 100 amino acids called a signal. The signal works as a molecular shipping label to direct the protein to its proper location.
Lysosomes are small, often spherical organelles that function as the cell’s recycling center and garbage disposal. Powerful digestive enzymes concentrated in the lysosome break down worn-out organelles and ship their building blocks to the cytoplasm where they are used to construct new organelles. Lysosomes also dismantle and recycle proteins, lipids, and other molecules.
The mitochondria is the powerhouses of the cell. Within these long, slender organelles, which can appear oval or bean shaped under the electron microscope, enzymes convert the sugar glucose and other nutrients into adenosine triphosphate (ATP). This molecule, in turn, serves as an energy battery for countless cellular processes, including the shuttling of substances across the plasma membrane, the building and transport of proteins and lipids, the recycling of molecules and organelles, and the dividing of cells. Muscle and liver cells are particularly active and require dozens and sometimes up to hundreds mitochondria per cell to meet their energy needs. Mitochondria is unusual in that they contain their own DNA in the form of a prokaryote-like circular chromosome; Have their own ribosomes, which resemble prokaryotic ribosomes, and divide independently of the cell.
Unlike the tiny prokaryotic cell, the relatively large eukaryotic cell requires structural support. The cytoskeleton, a dynamic network of protein tubes, filaments, and fibers, crisscrosses the cytoplasm, anchoring the organelles in place and providing shape and structure to the cell. Many components of the cytoskeleton are assembled and disassembled by the cell as needed. During cell division, for example, a special structure called a spindle is built to move chromosomes around. After cell division, the spindle, no longer needed, is dismantled. Some components of the cytoskeleton serve as microscopic tracks along which proteins and other molecules travel like miniature trains. Recent research suggests that the cytoskeleton also may be a mechanical communication structure that converses with the nucleus to help organize events in the cell.
Plant cells have all the components of animal cells and boast several added features, including chloroplasts, a central vacuole, and a cell wall. Chloroplasts convert light energy - typically from the Sun - into the sugar glucose, a form of chemical energy, in a process known as photosynthesis. Chloroplasts, like mitochondria, possess a circular chromosome and prokaryote-like ribosomes, which manufacture the proteins that the chloroplasts typically need.
The central vacuole of a mature plant cell typically takes up most of the room in the cell. The vacuole, a membranous bag, crowds the cytoplasm and organelles to the edges of the cell. The central vacuole stores water, salts, sugars, proteins, and other nutrients. In addition, it stores the blue, red, and purple pigments that give certain flowers their colors. The central vacuole also contains plant wastes that taste bitter to certain insects, thus discouraging the insects from feasting on the plant.
In plant cells, a sturdy cell wall surrounds and protects the plasma membrane. Its pores enable materials to pass freely into and out of the cell. The strength of the wall also enables a cell to absorb water into the central vacuole and swell without bursting. The resulting pressure in the cells provides plants with rigidity and support for stems, leaves, and flowers. Without sufficient water pressure, the cells collapse and the plant wilts.
CELL FUNCTIONS
To stay alive, cells must be able to carry out a variety of functions. Some cells must be able to move, and most cells must be able to divide. All cells must maintain the right concentration of chemicals in their cytoplasm, ingest food and use it for energy, recycle molecules, expel wastes, and construct proteins. Cells must also be able to respond to changes in their environment.
Although many forms of bacteria are not capable of independent movement, species such as the Salmonella bacterium pictured here can move by means of fine threadlike projections called flagella. The arrangement of flagella across the surface of the bacterium differs from species to species; they can be present at the ends of the bacterium or all across the body surface. Forward movement is accomplished either by a tumbling motion or in a forward manner without tumbling.
Many unicellular organisms swim, glide, thrash, or crawl to search for food and escape enemies. Swimming organisms often move by means of a flagellum, a long tail-like structure made of protein. Many bacteria, for example, have one, two, or many flagella that rotate like propellers to drive the organism along. Some single-celled eukaryotic organisms, such as euglena, also have a flagellum, but it is longer and thicker than the prokaryotic flagellum. The eukaryotic flagellums works by waving up and down like a whip. In higher animals, the sperm cell uses a flagellum to swim toward the female egg for fertilization.
Movement in eukaryotes is also accomplished with cilia, short, hairlike proteins built by centrioles, which are barrel-shaped structures located in the cytoplasm that assemble and break down protein filaments. Typically, thousands of cilia extend through the plasma membrane and cover the surface of the cell, giving it a dense, hairy appearance. By beating its cilia as if they were oars, an organism such as the paramecium propels itself through its watery environment. In cells that do not move, cilia are used for other purposes. In the respiratory tract of humans, for example, millions of ciliated cells prevent inhaled dust, smog, and microorganisms from entering the lungs by sweeping them up on a current of mucus into the throat, where they are swallowed. Eukaryotic flagella and cilia are formed from basal bodies, small protein structures located just inside the plasma membrane. Basal bodies also help to anchor flagella and cilia.
Still other eukaryotic cells, such as amoebas and white blood cells, move by amoeboid motion, or crawling. They extrude their cytoplasm to form temporary pseudopodia, or false feet, which actually are placed in front of the cell, rather like extended arms. They then drag the trailing end of their cytoplasm up to the pseudopodia. A cell using amoeboid motion would lose a race to a euglena or paramecium. But while it is slow, amoeboid motion is strong enough to move cells against a current, enabling water-dwelling organisms to pursue and devour prey, for example, or white blood cells roaming the blood stream to stalk and engulf a bacterium or virus.
An amoeba, a single-celled organism lacking internal organs, is shown approaching a much smaller paramecium, which it begins to engulf with large outflowings of its cytoplasm, called pseudopodia. Once the paramecium is completely engulfed, a primitive digestive cavity, called a vacuole, forms around it. In the vacuole, acids break the paramecium down into chemicals that the amoeba can diffuse back into its cytoplasm for nourishment.
All cells require nutrients for energy, and they display a variety of methods for ingesting them. Simple nutrients dissolved in pond water, for example, can be carried through the plasma membrane of pond-dwelling organisms via a series of molecular pumps. In humans, the cavity of the small intestine contains the nutrients from digested food, and cells that form the walls of the intestine use similar pumps to pull amino acids and other nutrients from the cavity into the bloodstream. Certain unicellular organisms, such as amoebas, are also capable of reaching out and grabbing food. They use a process known as endocytosis, in which the plasma membrane surrounds and engulfs the food particle, enclosing it in a sac, called a vesicle, that is within the amoeba’s interior.
Cells require energy for a variety of functions, including moving, building up and breaking down molecules, and transporting substances across the plasma membrane. Nutrients contain energy, but cells must convert the energy locked in nutrients to another form - specifically, the ATP molecule, the cell’s energy battery - before it is useful. In single-celled eukaryotic organisms, such as the paramecium, and in multicellular eukaryotic organisms, such as plants, animals, and fungi, mitochondria is responsible for this task. The interior of each mitochondrion consists of an inner membrane that is folded into a mazelike arrangement of separate compartments called cristae. Within the cristae, enzymes form an assembly line where the energy in glucose and other energy-rich nutrients is harnessed to build ATP; thousands of ATP molecules are constructed each second in a typical cell. In most eukaryotic cells, this process requires oxygen and is known as aerobic respiration.
Some prokaryotic organisms also carry out aerobic respiration. They lack mitochondria, however, and carry out aerobic respiration in the cytoplasm with the help of enzymes sequestered there. Many prokaryote species live in environments where there is little or no oxygen, environments such as mud, stagnant ponds, or within the intestines of animals. Some of these organisms produce ATP without oxygen in a process known as anaerobic respiration, where sulfur or other substances take the place of oxygen. Still other prokaryotes, and yeast, a single-celled eukaryote, build ATP without oxygen in a process known as fermentation.
Almost all organisms rely on the sugar glucose to produce ATP. Glucose is made by the process of photosynthesis, in which light energy is transformed to the chemical energy of glucose. Animals and fungi cannot carry out photosynthesis and depend on plants and other photosynthetic organisms for this task. In plants, as we have seen, photosynthesis takes place in organelles called chloroplasts. Chloroplasts contain numerous internal compartments called thylakoids where enzymes aid in the energy conversion process. A single leaf cell contains 40 to 50 chloroplasts. With sufficient sunlight, one large tree is capable of producing upwards of two tons of sugar in a single day. Photosynthesis in prokaryotic organisms - typically aquatic bacteria - is carried out with enzymes clustered in plasma membrane folds called chromatophores. Aquatic bacteria produce the food consumed by tiny organisms living in ponds, rivers, lakes, and seas.
bosomes
A typical cell must have on hand, about 30,000 proteins at any-one time. Many of these proteins are enzymes needed to construct the major molecules used by cells - carbohydrates, lipids, proteins, and nucleic acids - nor to aid in the breakdown of such molecules after they have worn out. Other proteins are part of the cell’s structure - the plasma membrane and ribosomes, for example. In animals, proteins also function as hormones and antibodies, and they function like delivery trucks to transport other molecules around the body. Hemoglobin, for example, is a protein that transports oxygen in red blood cells. The cell’s demand for proteins never ceases.
Before a protein can be made, however, the molecular directions to build it must be extracted from one or more genes. In humans, for example, one gene holds the information for the protein insulin, the hormone that cells need to import glucose from the bloodstream, while at least two genes hold the information for collagen, the protein that imparts strength to skin, tendons, and ligaments. The process of building proteins begins when enzymes, in response to a signal from the cell, bind to the gene that carries the code for the required protein, or part of the protein. The enzymes transfer the code to a new molecule called messenger RNA, which carries the code from the nucleus to the cytoplasm. This enables the original genetic code to remain safe in the nucleus, with messenger RNA delivering small bits and pieces of information from the DNA to the cytoplasm as needed. Depending on the cell type, hundreds or even thousands of molecules of messenger RNA are produced each minute.
Once in the cytoplasm, the messenger RNA molecule links up with a ribosome. The ribosome moves along the messenger RNA like a monorail car along a track, stimulating another form of RNA - transfer RNA - to gather and link the necessary amino acids, pooled in the cytoplasm, to form the specific protein, or section of protein. The protein is modified as necessary by the endoplasmic reticulum and Golgi apparatus before embarking on its mission. Cells teem with activity as they forge the numerous, diverse proteins that are indispensable for life. For a more detailed discussion about protein synthesis, When there are a hundred or more cells, they formed a hollow ball of cells, called a blastula, surrounding a fluid-filled cavity. Later divisions produce three layers of cells - endoderm (inner), mesoderm (middle), and ectoderm (outer) - from which the principal features of the animal will differentiate.
Most cells divide at some time during their life cycle, and some divide dozens of times before they die. Organisms rely on cell division for reproduction, growth, and repair and replacement of damaged or worn out cells. Three types of cell division occur: Binary fission, mitosis, and meiosis. Binary fission, the method used by prokaryotes, produces two identical cells from one cell. The more complex process of mitosis, which also produces two genetically identical cells from a single cell, is used by many unicellular eukaryotic organisms for reproduction. Multicellular organisms use mitosis for growth, cell repair, and cell replacement. In the human body, for example, an estimated 25 million mitotic cell divisions occur every second in order to replace cells that have completed their normal life cycles. Cells of the liver, intestine, and skin may be replaced every few days. Recent research indicates that even brain cell, once thought to be incapable of mitosis, undergo cell division in the part of the brain associated with memory.
In a landmark intersection of science and fiction, cloning leapt from the world’s imagination to its front page in February 1997. It arrived in the innocent form of a sheep named Dolly: The first exact genetic duplicate of an adult mammal due to genetic engineering. Scottish scientists had created Dolly from deoxyribonucleic acid (DNA) - the basic unit of heredity - taken from a single adult sheep cell. The accomplishment threw open the door to profound ethical as well as scientific controversy over the potential uses and abuses of cloning. “However the debate is resolved,” wrote Los Angeles Times science reporter Thomas H. Maugh II, “the genie is irretrievably out of the bottle.”
The type of cell division required for sexual reproduction is meiosis. Sexually reproducing organisms include seaweeds, fungi, plants, and animals - including, of course, human beings. Meiosis differs from mitosis in that cell division begins with a cell that has a full complement of chromosomes and ends with gamete cells, such as sperm and eggs, that have only half the complement of chromosomes. When a sperm and egg unite during fertilization, the cell resulting from the union, called a zygote, contains the full number of chromosomes.
The story of how cells evolved remains an open and actively investigated question in science. The combined expertise of physicists, geologists, chemists, and evolutionary biologists has been required to shed light on the evolution of cells from the nonliving matter of early Earth. The planet formed about 4.5 billion years ago, and for millions of years, violent volcanic eruptions blasted substances such as carbon dioxide, nitrogen, water, and other small molecules into the air. These small molecules, bombarded by ultraviolet radiation and lightning from intense storms, collided to form the stable chemical bonds of larger molecules, such as amino acids and nucleotides - the building blocks of proteins and nucleic acids. Experiments indicate that these larger molecules form spontaneously under laboratory conditions that simulate the probable early environment of Earth.
Scientists speculate that rain may have carried these molecules into lakes to create a primordial soup - the breeding ground for the assembly of proteins, the nucleic acid RNA, and lipids. Some scientists postulate that these more complex molecules formed in hydrothermal vents rather than in lakes. Other scientists propose that these key substances may have reached Earth on meteorites from outer space. Regardless of the origin or environment, however, scientists do agree that proteins, nucleic acids, and lipids provided the raw materials for the first cells. In the laboratory, scientists have observed lipid molecules joining to form spheres that resemble a cell’s plasma membrane. As a result of these observations, scientists postulate that millions of years of molecular collisions resulted in lipid spheres enclosing RNA, the simplest molecule capable of self-replication. These primitive aggregations would have been the ancestors of the first prokaryotic cells.
Fossil studies indicate that cyanobacteria, bacteria capable of photosynthesis, were among the earliest bacteria to evolve, an estimated 3.4 billion to 3.5 billion years ago. In the environment of the early Earth, there were no oxygen, and cyanobacteria probably used fermentation to produce ATP. Over the eons, cyanobacteria performed photosynthesis, which produces oxygen as a byproduct; The result was the gradual accumulation of oxygen in the atmosphere. The presence of oxygen set the stage for the evolution of bacteria that used oxygen in aerobic respiration, a more efficient ATP-producing process than fermentation. Some molecular studies of the evolution of genes in archaebacteria suggest that these organisms may have evolved in the hot waters of hydrothermal vents or hot springs slightly earlier than cyanobacteria, around 3.5 billion years ago. Like cyanobacteria, archaebacteria probably relied on fermentation to synthesize ATP.
Eukaryotic cells may have evolved from primitive prokaryotes about 2 billion years ago. One hypothesis suggests that some prokaryotic cells lost their cell walls, permitting the cell’s plasma membrane to expand and fold. These folds, ultimately, may have given rise to separate compartments within the cell - the forerunners of the nucleus and other organelles now found in eukaryotic cells. Another key hypothesis is known as endosymbiosis. Molecular studies of the bacteria-like DNA and ribosomes in mitochondria and chloroplasts indicate that mitochondrion and chloroplast ancestors were once free-living bacteria. Scientists propose that these free-living bacteria were engulfed and maintained by other prokaryotic cells for their ability to produce ATP efficiently and to provide a steady supply of glucose. Over generations, eukaryotic cells situated with mitochondria - the ancestors of animals - or with both mitochondria and chloroplasts - the ancestors of plants - evolved.
The first observations of cells were made in 1665 by English scientist Robert Hooke, who used a crude microscope of his own invention to examine a variety of objects, including a thin piece of cork. Noting the rows of tiny boxes that made up the dead wood’s tissue, Hooke coined the term cell because the boxes reminded him of the small cells occupied by monks in a monastery. While Hooke was the first to observe and describe cells, he did not comprehend their significance. At about the same time, the Dutch maker of microscopes Antoni van Leeuwenhoek pioneered the invention of one of the best microscopes of the time. Using his invention, Leeuwenhoek was the first to observe, draw, and describe a variety of living organisms, including bacteria gliding in saliva, one-celled organisms cavorting in pond water, and sperm swimming in semen. Two centuries passed, however, before scientists grasped the true importance of cells.
Many advances have been made in microscope technology. This article from the 1994 Collier’s Year Book begins with the microscope most young students are familiar with and tracks the breakthroughs in the development of new types of microscopes - including those that use ultrasonic imaging and those that “feel” an object’s surface.
Modern ideas about cells appeared in the 1800s, when improved light microscopes enabled scientists to observe more details of cells. Working together, German botanist Matthias Jakob Schleiden and German zoologist Theodor Schwann recognized the fundamental similarities between plant and animal cells. In 1839 they proposed the revolutionary idea that all living things are made up of cells. Their theory gave rise to modern biology: a whole new way of seeing and investigating the natural world.
By the late 1800s, as light microscopes improved still further, scientists were able to observe chromosomes within the cell. Their research was aided by new techniques for staining parts of the cell, which made possible the first detailed observations of cell division, including observations of the differences between mitosis and meiosis in the 1880s. In the first few decades of the 20th century, many scientists focused on the behavior of chromosomes during cell division. At that time, it was generally held that mitochondria transmitted the hereditary information. By 1920, however, scientists determined that chromosomes carry genes and that genes transmit hereditary information from generation to generation.
During this period, scientists began to understand some of the chemical processes in cells. In the 1920s, the ultracentrifuge was developed. The ultracentrifuge is an instrument that spins cells or other substances in test tubes at high speeds, which causes the heavier parts of the substance to fall to the bottom of the test tube. This instrument enabled scientists to separate the relatively abundant and heavy mitochondria from the rest of the cell and study their chemical reactions. By the late 1940s, scientists were able to explain the role of mitochondria in the cell. Using refined techniques with the ultracentrifuge, scientists subsequently isolated the smaller organelles and gained an understanding of their functions.
The deoxyribonucleic acid (DNA) molecule is the genetic blueprint for each cell and ultimately the blueprint that determines every characteristic of a living organism. In 1953 American biochemist James Watson, left, and British biophysicist Francis Crick, right, described the structure of the DNA molecule as a double helix, somewhat like a spiral staircase with many individual steps. Their work was aided by X-ray diffraction pictures of the DNA molecule taken by British biophysicist Maurice Wilkins and British physical chemist Rosalind Franklin. In 1962 Crick, Watson, and Wilkins received the Nobel Prize for their pioneering work on the structure of the DNA molecule.
While some scientists were studying the functions of cells, others were examining details of their structure. They were aided by a crucial technological development in the 1940s, the invention of the electron microscope, which uses high-energy electrons instead of light waves to view specimens. New generations of electron microscopes have provided resolution, or the differentiation of separate objects, thousands of times more powerful than that available in light microscopes. This powerful resolution revealed organelles such as the endoplasmic reticulum, lysosomes, the Golgi apparatus, and the cytoskeleton. The scientific fields of cell structure and function continue to complement each other as scientists explore the enormous complexity of cells.
The discovery of the structure of DNA in 1953 by American biochemist James D. Watson and British biophysicist Francis Crick ushered in the era of molecular biology. Today, investigation inside the world of cells - of genes and proteins at the molecular level - constitutes one of the largest and fastest moving areas in all of science. One particularly active field in recent years has been the investigation of cell signaling, the process by which molecular messages find their way into the cell via a series of complex protein pathways in the cell.
Another busy area in cell biology concerns programmed cell death, or apoptosis. Millions of times per second in the human body, cells commit suicide as an essential part of the normal cycle of cellular replacement. This also seems to be a check against disease: When mutations build up within a cell, the cell will usually self-destruct. If this fails to occur, the cell may divide and give rise to mutated daughter cells, which continue to divide and spread, gradually forming a growth called a tumor. This unregulated growth by rogue cells can be benign, or harmless, or cancerous, which may threaten healthy tissue. The study of apoptosis is one avenue that scientists explore in an effort to understand how cells become cancerous.
Scientists are also discovering exciting aspects of the physical forces within cells. Cells employ a form of architecture called tensegrity, which enables them to withstand battering by a variety of mechanical stresses, such as the pressure of blood flowing around cells or the movement of organelles within the cell. Tensegrity stabilizes cells by evenly distributing mechanical stresses to the cytoskeleton and other cell components. Tensegrity also may explain how a change in the cytoskeleton, where certain enzymes are anchored, initiates biochemical reactions within the cell, and can even influence the action of genes. The mechanical rules of tensegrity may also account for the assembly of molecules into the first cells. Such new insights - made some 300 years after the tiny universe of cells was first glimpsed - show that cells continue to yield fascinating new worlds of discovery.
The Nervous System
The Nervous System signifies of those elements within the animal organism that are concerned with the reception of stimuli, the transmission of nerve impulses, or the activation of muscle mechanisms.
The reception of stimuli is the function of special sensory cells. The conducting elements of the nervous system are cells called neurons; these may be capable of only slow and generalized activity, or they may be highly efficient and rapidly conducting units. The specific response of the neuron—the nerve impulse - and the capacity of the cell to be stimulated make this cell a receiving and transmitting unit capable of transferring information from one part of the body to another.
Each nerve cell consists of a central portion containing the nucleus, known as the cell body, and one or more structures referred to as axons and dendrites. The dendrites are rather short extensions of the cell body and are involved in the reception of stimuli. The axon, by contrast, is usually a single elongated extension, it is especially important in the transmission of nerve impulses from the region of the cell body to other cells.
Although all many-celled animals have some kind of nervous system, the complexity of its organization varies considerably among different animal types. In simple animals such as jellyfish, the nerve cells form a network capable of mediating only a relatively stereotyped response. In more complex animals, such as shellfish, insects, and spiders, the nervous system is more complicated. The cell bodies of neurons are organized in clusters called ganglia. These clusters are interconnected by the neuronal processes to form a ganglionated chain. Such chains are found in all vertebrates, in which they represent a special part of the nervous system, related especially to the regulation of the activities of the heart, the glands, and the involuntary Vertebrate animals have a bony spine and skull in which the central part of the nervous system is housed; The peripheral part extends throughout the remainder of the body. That part of the nervous system located in the skull is referred to as the brain, that found in the spine is called the spinal cord. The brain and the spinal cord are continuous through an opening in the base of the skull; Both are also in contact with other parts of the body through the nerves. The distinction made between the central nervous system and the peripheral nervous system is based on the different locations of the two intimately related parts of a single system. Some of the processes of the cell bodies conduct sense impressions and others conduct muscle responses, called reflexes, such as those caused by pain.
In the skin are cells of several types called receptors; each is especially sensitive to particular stimuli. Free nerve endings are sensitive to pain and are directly activated. The neurons so activated send impulses into the central nervous system and have junctions with other cells that have axons extending back into the periphery. Impulses are carried from processes of these cells to motor endings within the muscles. These neuromuscular endings excite the muscles, resulting in muscular contraction and appropriate movement. The pathway taken by the nerve impulse in mediating this simple response is in the form of a two-neuron arc that begins and ends in the periphery. Many of the actions of the nervous system can be explained on the basis of such reflex arcs, which are chains of interconnected nerve cells, stimulated at one end and capable of bringing about movement or glandular secretion at the other.
The cranial nerves connect to the brain by passing through openings in the skull, or cranium. Nerves associated with the spinal cord pass through openings in the vertebral column and are called spinal nerves. Both cranial and spinal nerves consist of large numbers of processes that convey impulses to the central nervous system and also carry messages outward; the former processes are called afferent, the latter are called efferent. Afferent impulses are referred to as sensory; efferent impulses are referred to as either somatic or visceral motor, according to what part of the body they reach. Most nerves are mixed nerves made up of both sensory and motor elements.
The cranial and spinal nerves are paired; The number in humans are 12 and 31, respectively. Cranial nerves are distributed to the head and neck regions of the body, with one conspicuous exception: the tenth cranial nerve, called the vagus. In addition to supplying structures in the neck, the vagus is distributed to structures located in the chest and abdomen. Vision, auditory and vestibular sensation, and taste is mediated by the second, eighth, and seventh cranial nerves, respectively. Cranial nerves also mediate motor functions of the head, the eyes, the face, the tongue, and the larynx, as well as the muscles that function in chewing and swallowing. Spinal nerves, after they exit from the vertebrae, are distributed in a band-like fashion to regions of the trunk and to the limbs. They interconnect extensively, thereby forming the brachial plexus, which runs to the upper extremities, and the lumbar plexus, which passes to the lower limbs.
Among the motor fibers may be found groups that carry impulses to viscera. These fibers are designated by the special name of autonomic nervous system. That system consists of two divisions, more or less antagonistic in function, that emerge from the central nervous system at different points of origin. One division, the sympathetic, arises from the middle portion of the spinal cord, joins the sympathetic ganglionated chain, courses through the spinal nerves, and is widely distributed throughout the body. The other division, the parasympathetic, arises both above and below the sympathetic, that is, from the brain and from the lower part of the spinal cord. These two divisions control the functions of the respiratory, circulatory, digestive, and urogenital systems.
Consideration of disorders of the nervous system is the province of neurology; Psychiatry deals with behavioral disturbances of a functional nature. The division between these two medical specialties cannot be sharply defined, because neurological disorders often manifest both organic and mental symptoms.
Diseases of the nervous system include genetic malformations, poisonings, metabolic defects, vascular disorders, inflammations, degeneration, and tumors, and they involve either nerve cells or their supporting elements. Vascular disorders, such as cerebral hemorrhage or other forms of a stroke, are among the most common causes of paralysis and other neurologic complications. Some diseases exhibit peculiar geographic and age distribution. In temperate zones, multiple sclerosis is a common degenerative disease of the nervous system, but it is rare in the Tropics.
The nervous system is subject to infection by a great variety of bacteria, parasites, and viruses. For example, meningitis, or infection of the meninges investing the brain and spinal cord, can be caused by many different agents. On the other hand, one specific virus causes rabies. Some viruses causing neurological ills affect only certain parts of the nervous system. For example, the virus causing poliomyelitis commonly affects the spinal cord, as Viruses manufacturing encephalitis attack the brain.
Inflammations of the nervous system are named according to the part affected. Myelitis is an inflammation of the spinal cord; Neuritis is an inflammation of a nerve. It may be caused not only by infection but also by poisoning, alcoholism, or injury. Tumors originating in the nervous system usually are composed of meningeal tissue or neuroglia (supporting tissue) cells, depending on the specific part of the nervous system affected, but other types of a tumor may metastasize to or invade the nervous system. In certain disorders of the nervous system, such as neuralgia, migraine, and epilepsy, no evidence may exist of organic damage. Another disorder, cerebral palsy, is associated with birth defects.
PHYSIOLOGY of PAIN
Pain, an unpleasant sensory and emotional experience caused by real or potential injury or damage to the body or described in terms of such damage. Scientists believe that pain evolved in the animal kingdom as a valuable three-part warning system. First, it warns of injury. Second, pain protects against further injury by causing a reflexive withdrawal from the source of injury. Finally, pain leads to a period of reduced activity, enabling injuries to heal more efficiently.
Pain is difficult to measure in humans because it has an emotional, or psychological component as well as a physical component. Some people express extreme discomfort from relatively small injuries, while others show little or no pain even after suffering severe injury. Sometimes pain is present even though no injury is apparent at all, or pain lingers long after an injury appears to have healed.
The signals that warn the body of tissue damage are transmitted through the nervous system. In this system, the basic unit is the nerve cell or neuron. A nerve cell is composed of three parts: a central cell body, a single major branching fiber called an axon, and a series of smaller branching fibers known as dendrites. Each nerve cell meets other nerve cells at certain points on the axons and dendrites, forming a dense network of interconnected nerve fibers that transmit sensory information about touch, pressure, or warmth, as well as pain.
Sensory information is transmitted from the different parts of the body to the brain via the spinal cord, which is a complex set of nerves that extend from the brain down along the back, protected by the bones of the spine. About as wide as a finger, the spinal cord is like a cable packed with many bundles of wires. The bundles are nerve pathways for transmitting information. But the spinal cord is more than just a message transmitter, it is also an extension of the brain. It contains neurons that process incoming sensory information, and generates messages to be sent back down to cells in other parts of the body.
In the nervous system, a message-carrying impulse travels from one end of a nerve cell to the other by means of an electrical impulse. When it reaches the terminal end of a nerve cell, the impulse triggers tiny sacs called presynaptic vessicles to release their contents, chemical messengers called neurotransmitters. The neurotransmitters float across the synapse, or gap between adjacent nerve cells. When they reach the neighboring nerve cell, the neurotransmitters fit into specialized receptor sites much as a key fits into a lock, causing that nerve cell to “fire,” or generate an electric message-carrying impulse. As the message continues through the nervous system, the presynaptic cell absorbs the excess neurotransmitters, and repackages them in presynaptic versicles in a process called neurotransmitter reuptake.
Information being transmitted between and within the brain and spinal cord travels through the nervous system using both chemical and electrical mechanisms. A message-carrying impulse travels from one end of a nerve cell to another by means of an electric signal. When the electric signal reaches the terminal end of a nerve cell, a gap called a synapse prevents the electric signal from crossing to the next cell. The electric signal triggers the cell to release chemicals called neurotransmitters, which float across the synapse to the neighboring nerve cell. These neurotransmitters fit into specialized receptors found on the adjacent nerve cell, much as a key fits into a lock, generating an electric impulse in the neighboring cell. This new impulse travels to the end of the long cell, in turn triggering the release of neurotransmitters to carry the message across the next synapse. Not all neurotransmitters initiate a message in a neighboring nerve cell. Some specialize in preventing neighboring cells from generating an electrical signal, while others function as helpers, facilitating the message's journey to the brain.
While most of the sensory nerves in the skin and other body tissues have special structures covering their nerve endings, those nerves that signal injury have free nerve endings. These simple nerve endings specialize in detecting noxious stimuli - a catchall term for injury-causing stimuli such as intense heat, extreme pressure, or sharp pricks or cuts. The nerve endings that detect pain are called nociceptors, and the process of transmitting pain signals when harmful stimulation occurs is called nociception. Several million nociceptors are interlaced through the tissues and organs of the body.
When a person experiences an injury, such as a stubbed toe, specialized cells called nociceptors sense potential tissue damage (1) and send an electric signal, called an impulse, to the spinal cord via a sensory nerve (2). A specialized region of the spinal cord known as the dorsal horn (3) processes the pain signal, immediately sending another impulse back down the leg via a motor nerve (4). This causes the muscles in the leg to contract and pull the toe away from the source of injury (6). At the same time, the dorsal horn sends another impulse up the spinal cord to the brain. During this trip, the impulse travels between nerve cells. When the impulse reaches a nerve ending (7), the nerve released chemical messengers, called neurotransmitters, which carry the message to the adjacent nerve. When the impulse reaches the brain (8), it is analyzed and processed as an unpleasant physical and emotional sensation.
An injury triggers pain signals in two types of nociceptors, one with large, insulated axons known as A-delta fibers and one with small, uninsulated axons known as C fibers. The large A-delta fibers conduct signals quickly, and the smaller C fibers transmit information slowly. The difference in the functions of these two fibers becomes obvious to a person who stubs a toe. At first the injured person is aware of a sharp, flashing pain at the point of injury. Generated by the A-delta fibers, this short-lived pain intrudes upon the thoughts and perceptions occurring in the brain. Just as this first pain subsides, a second pain begins that is vague, throbbing, and persistent. This sensation is derived from the C fibers.
Pain information from the A-delta and C fibers travels through the spinal cord to the brain. When it receives the pain message, the spinal cord generates impulses that travel back down to muscles, which lead to a reflexive contraction that pulls the body away from the source of injury. Other reflexes may affect skin temperature, blood flow, sweating, and other changes.
While this reflex action is underway, the pain message continues up the spinal cord to relay centers in the brain. The sensory information is routed to many other parts of the brain, including the cortex, where thinking processes occur
Adrenal Gland
The Adrenal Gland is the vital endocrine gland that secretes hormones into the bloodstream, situated, in humans, on top of the upper end of each kidney. The two parts of the gland - the inner portion, or medulla, and the outer portion, or the cortex - are like separate organs: They are composed of different types of tissue and perform different functions. The adrenal medulla, composed of chromaffin cells secretes the hormone epinephrine, also called adrenaline, in response to stimulation of the sympathetic nervous system at times of stress. The medulla also secretes the hormone norepinephrine, which plays a role in maintaining normal blood circulation. The hormones of the medulla are called catecholamines. Unlike the adrenal cortex, the medulla can be removed without endangering the life of an individual.
The adrenal outer layer, or cortex, secretes about 30 steroid hormones, but only a few are secreted in significant amounts. Aldosterone, one of the most important hormones, regulates the balance of salt and water in the body. Cortisone and hydrocortisone are necessary to regulate fat, carbohydrate, and protein metabolism. Adrenal sex steroids have a minor influence on the reproductive system. Modified steroids, now produced synthetically, are superior to naturally secreted steroids for treatment of Addison's disease and other disorders.
Adrenocorticotropic Hormone
Adrenocorticotropic Hormone is also known as corticotropin, hormones secreted by the anterior part of the pituitary gland. The specific function of ACTH is to stimulate the growth and secretions of the cortex (outer layers) of the adrenal gland. One of these secretions is cortisone, a hormone involved in carbohydrate and protein metabolisms. ACTH is used medically for its anti-inflammatory action to alleviate symptoms of allergies and arthritis. ACTH is a complex protein molecule containing 39 amino acids. Its molecular weight is approximately 5000. The biological activity of the ACTH of various animal species is similar to that of humans, but the sequence of amino acids has been found to vary somewhat among species. ACTH production is controlled in part by the hypothalamus and in part by the existing levels of adrenal gland hormones. ACTH levels increased in response to stress, disease, and decreased blood pressure.
PITUITARY GLAND
The Pituitary Gland is the master endocrine gland in vertebrate animals. The hormones secreted by the pituitary stimulate and control the functioning of almost all the other endocrine glands in the body. Pituitary hormones also promote growth and control the water balance of the body.
The pituitary is a small bean-shaped, reddish-gray organ located in the saddle-shaped depression (sella turcica) in the floor of the skull (the sphenoid bone) and attached to the base of the brain by a stalk; it is located near the hypothalamus. The pituitary has two lobes - the anterior lobe, or adenohypophysis, and the posterior lobe, or neurohypophysis - which differ in structure and function. The anterior lobe is derived embryologically from the roof of the pharynx and is composed of groups of epithelial cells separated by blood channels; the posterior lobe is derived from the base of the brain and is composed of nervous connective tissue and nerve-like secreting cells. The area between the anterior and posterior lobes of the pituitary is called the intermediate lobe; it has the same embryological origin as the anterior lobe.
Concentrated chemical substances, or hormones, which control 10 to 12 functions in the body, have been obtained as extracts from the anterior pituitary glands of cattle, sheep, and swine. Eight hormones have been isolated, purified, and identified; All of them are peptides, that is, they are composed of amino acids. A growth hormone (GH), or the somatotropic hormone (STH), is essential for normal skeletal growth and is neutralized during adolescence by the gonadal sex hormones. Thyroid-stimulating hormones (TSH) control the normal functioning of the thyroid gland, and the adrenocorticotropic hormone (ACTH) controls the activity of the cortex of the adrenal glands and takes part in the stress reaction. Prolactin, also called lactogenic, luteotropic, or mammotropic hormone, initiates milk secretion in the mammary gland after the mammary tissues have been prepared during pregnancy by the secretion of other pituitary and sex hormones. The two gonadotropic hormones are follicle-stimulating hormones (FSH) and a luteinizing hormone (LH). Follicle-stimulating hormones stimulates the formation of the Graafian follicle in the female ovary and the development of spermatozoa in the male. The luteinizing hormone stimulates the formation of ovarian hormones after ovulation and initiates lactation in the female, in the male, it stimulates the tissues of the testes to elaborate testosterone. In 1975 scientists identified the pituitary peptide endorphin, which acts in experimental animals as a natural pain reliever in times of stress. Endorphin and ACTH are made as parts of a single large protein, which subsequently splits. This may be the body's mechanism for coordinating the physiological activities of two stress-induced hormones. The same large prohormone that contains ACTH and endorphin also contains short peptides called melanocyte-stimulating hormones. These substances are analogous to the hormone that regulates pigmentation in fish and amphibians, but in humans they have no known function.
Research has shown that the hormonal activity of the anterior lobe is controlled by chemical messengers sent from the hypothalamus through tiny blood vessels to the anterior lobe. In the 1950s, the British neurologist Geoffrey Harris discovered that cutting the blood supply from the hypothalamus to the pituitary impaired the function of the pituitary. In 1964, chemical agents called releasing factors were found in the hypothalamus; These substances, it was learned, affect the secretion of growth hormone, a thyroid-stimulating hormone called thyrotropin, and the gonadotropic hormones involving the testes and ovaries. In 1969 the American endocrinologist Roger Guillemin and colleagues isolated and characterized thyrotropin-releasing factors, which stimulates the secretion of thyroid-stimulating hormone from the pituitary. In the next few years his group and that of the American physiologist Andrew Victor Schally isolated the luteinizing hormone-releasing factor, which stimulates secretion of both LH and FSH, and somatostatin, which inhibits release of growth hormone. For this work, which proved that the brain and the endocrine system are linked, they shared the Nobel Prize in physiology or medicine in 1977. Human somatostatin was one of the first substances to be grown in bacteria by recombinant DNA.
The presence of the releasing factors in the hypothalamus helped to explain the action of the female sex hormones, estrogen and progesterone, and their synthetic versions contained in oral contraceptives, or birth-control pills. During a woman's normal monthly cycle, several hormonal changes are needed for the ovary to produce an egg cell for possible fertilization. When the estrogen level in the body declines, the follicle-releasing factor (FRF) flows to the pituitary and stimulates the secretion of the follicle-stimulating hormone. Through a similar feedback principle, the declining level of progesterone causes a release of luteal-releasing factors (LRF), which stimulates secretion of the luteinizing hormone. The ripening follicle in the ovary then produces estrogen, and the high level of that hormone influences the hypothalamus to shut down temporarily the production of FSH. Increased progesterone feedback to the hypothalamus shuts down LH production by the pituitary. The daily doses of synthetic estrogen and progesterone in oral contraceptives, or injections of the actual hormones, inhibit the normal reproductive activity of the ovaries by mimicking the effect of these hormones on the hypothalamus.
In lower vertebrates this part of the pituitary secretes melanocyte-stimulating hormones, which brings about skin-color changes. In humans, it is present only for a short time early in life and during pregnancy, and is not known to have any function.
Two hormones are secreted by the posterior lobe. One of these is the antidiuretic hormone (ADH), vasopressin. Vasopressin stimulates the kidney tubules to absorb water from the filtered plasma that passes through the kidneys and thus controls the amount of urine secreted by the kidneys. The other posterior pituitary hormone is oxytocin, which causes the contraction of the smooth muscles in the uterus, intestines, and blood arterioles. Oxytocin stimulates the contractions of the uterine muscles during the final stage of pregnancy to stimulate the expulsion of the fetus, and it also stimulates the ejection, or let-down, of milk from the mammary gland following pregnancy. Synthesized in 1953, oxytocin was the first pituitary hormone to be produced artificially. Vasopressin was synthesized in 1956.
Pituitary functioning may be disturbed by such conditions as tumors, blood poisoning, blood clots, and certain infectious diseases. Conditions resulting from a decrease in anterior-lobe secretion include dwarfism, acromicria, Simmonds's disease, and Fröhlich's syndrome. The dwarfism occurs when anterior pituitary deficiencies occur during childhood; acromicria, in which the bones of the extremities are small and delicate, results when the deficiency occurs after puberty. Simmonds's disease, which is caused by extensive damage to the anterior pituitary, is characterized by premature aging, loss of hair and teeth, anemia, and emaciation; it can be fatal. Fröhlich's syndrome, also called adiposogenital dystrophy, is caused by both anterior pituitary deficiency and a lesion of the posterior lobe or hypothalamus. The result is obesity, dwarfism, and retarded sexual development. Glands under the influence of anterior pituitary hormones are also affected by anterior pituitary deficiency.
Over secretion of one of the anterior pituitary hormones, somatotropin, results in a progressive chronic disease called acromegaly, which is characterized by enlargement of some parts of the body. Posterior-lobe deficiency results in diabetes insipidus.
Tissue
Tissue, - group of associated, similarly structured cells that perform specialized functions for the survival of the organism. Animal tissues, to which this article is limited, take their first form when the blastula cells, arising from the fertilized ovum, differentiate into three germ layers: the ectoderm, mesoderm, and endoderm. Through further cell differentiation, or histogenesis, groups of cells grow into more specialized units to form organs made up, usually, of several tissues of similarly performing cells. Animal tissues are classified into four main groups.
These tissues include the skin and the inner surfaces of the body, such as those of the lungs, stomach, intestines, and blood vessels. Because its primary function is to protect the body from injury and infection, epitheliums are made up of tightly packed cells with little intercellular substance between them.
About 12 kinds of epithelial tissue occur. One kind is stratified squamous tissue found in the skin and the linings of the esophagus and vagina. It is made up of thin layers of flat, scalelike cells that form rapidly above the blood capillaries and is pushed toward the tissue surface, where they die and are shed. Another is a simple columnar epithelium, which lines the digestive system from the stomach to the anus; Simple columnar epithelium cells stand upright and not only control the absorption of nutrients but also secrete mucus through individual goblet cells. Glands are formed by the inward growth of epithelium-for examples, the sweat glands of the skin and the gastric glands of the stomach. Outward growth results in hair, nails, and other structures.
These tissues, which support and hold parts of the body together, comprises the fibrous and elastic connective tissues, the adipose (fatty) tissues, and cartilage and bone. In contrast to an epithelium, the cells of these tissues are widely separated from one another, with a large amount of intercellular substance between them. The cells of fibrous tissue, found throughout the body, connect to one another by an irregular network of strands, forming a soft, cushiony layer that also supports blood vessels, nerves, and other organs. Adipose tissue has a similar function, except that its fibroblasts also contain store fat. Elastic tissue, found in ligaments, the trachea, and the arterial walls, stretches and contracts again with each pulse beat. In the human embryo, the fibroblast cells that originally secreted collagen for the formation of fibrous tissue later change to secrete a different form of protein called chondrion, for the formation of cartilage, some cartilage later becomes calcified by the action of osteoblast to form bones. Blood and lymph are also often considered connective tissues.
Tissues, which contract and relax, comprise the striated, smooth, and cardiac muscles. Striated muscles, also called skeletal or voluntary muscles, include those that are activated by the somatic, or voluntary, nervous system. They are joined together without cell walls and have several nuclei. The smooth, or involuntary muscles, which are activated by the autonomic nervous system, are found in the internal organs and consist of simple sheets of cells. Cardiac muscles, which have characteristics of both striated and smooth muscles, are joined together in a vast network. These highly complex groups of cells, called ganglia, transfer information from one part of the body to another. Each neuron, or nerve cell, consists of a cell body with branching dendrites and one long fiber, or axons. The dendrites connect one neuron to another; The axon transmits impulses to an organ or collects impulses from a sensory organ.
Crossing a Synapse
In the nervous system, a message-carrying impulse travels from one end of a nerve cell to the other by means of an electrical impulse. When it reaches the terminal end of a nerve cell, the impulse trigger’s tiny sacs called presynaptic vessicles to release their contents, chemical messengers called neurotransmitters. The neurotransmitters float across the synapse, or gap between adjacent nerve cells. When they reach the neighboring nerve cell, the neurotransmitters fit into specialized receptor sites much as a key fits into a lock, causing that nerve cell to fire or generate an electric message-carrying impulse. As the message continues through the nervous system, the presynaptic cell absorbs the excess neurotransmitters, and repackages them in presynaptic versicles in a process called neurotransmitter reuptake.
Reflex
Reflex, in physiology, is the involuntary response to a stimulus by the animal organism. In its simplest form, it consisted of the stimulation of an afferent nerve through a sense organ, or receptor, followed by transmission of the stimulus, usually through a nerve center, to an efferent motor nerve, resulting in action of a muscle or gland, called the effector. In most reflex action, however, the stimulus passes through one or more intermediate nerve cells, which modify and direct its action, sometimes to the extent of involving the muscular activity of the entire organism. For example, a painful stimulus applied to the hand causes a reflex withdrawal of the hand, which involves contraction of the flexor group of muscles and reflexation of the opposing extensor group; if the stimulus is strong, the coordinating nerve cells pass it to the arm muscles and also to the muscles of the trunk and legs, the result being a jump that removes not only the arm, but the entire person from the vicinity of the painful stimulus.
The system of coordinating nerve cells is such that several different kinds of stimuli may produce the same result. For example, the stimulus produced by the sight of food and that caused by the smell of food travel different afferent pathways, but both have a common final path that stimulates the salivary glands to secretion. The final common path may also be activated through associated nerve tracts by a stimulus that ordinarily is not directly connected with the response. This type of reflex was named conditioned reflex by its discoverer, the Russian physiologist Ivan Pavlov, about 1904. Pavlov found that sounding a bell every time a dog was about to be given food eventually caused a reflex flow of saliva, which later persisted even when no food was produced. Elaborations of this habituative type of reflex are regarded by some physiologists and psychologists as an important basis for many behaviors, both voluntary and involuntary.
The normal pathways of many reflexes are generally known, and the presence, absence, or exaggerations of the normal physical responses to certain stimuli are symptoms used by neurologists to determine the condition of the neural pathways involved. A familiar reflex commonly tested by physicians is the patellar reflex, in which an involuntary jerk of the knee is evoked by lightly striking the tendon of the patella, or kneecap, indicating the efficiency of certain nerve tracts in the spinal cord.
Like all other cells, neurons contain charged ions: Potassium and sodium (positively charged) and chlorine (negatively charged). Neurons differ from other cells in that they are able to produce a nerve impulse. A neuron is polarized - that is, it has an overall negative charge inside the cell membrane because of the high concentration of chlorine ions and low concentration of potassium and sodium ions. The concentration of these same ions is exactly reversed outside the cell. This charge differential represents stored electrical energy, sometimes referred to as membrane potential or resting potential. The negative charge inside the cell is maintained by two features. The first is the selective permeability of the cell membrane, which is more permeable to potassium than sodium. The second feature is sodium pumps within the cell membrane that actively pump sodium out of the cell. When depolarization occurs, this charge differential across the membrane is reversed, and a nerve impulse is produced.
Depolarization is a rapid change in the permeability of the cell membrane. When sensory input or any other kind of stimulating current is received by the neuron, the membrane permeability is changed, allowing a sudden influx of sodium ions into the cell. The high concentration of sodium, or action potential, changes the overall charge within the cell from negative to positive. The local changes in ion concentration triggers similar reactions along the membrane, propagating the nerve impulse. After a brief period called the refractory period, during which the ionic concentration returned to resting potential, the neuron can repeat this process.
Nerve impulses travel at different speeds, depending on the cellular composition of a neuron. Where speed of impulse is important, as in the nervous system, axons are insulated with a membranous substance called myelin. The insulation provided by myelin maintains the ionic charge over long distances. Nerve impulses are propagated at specific points along the myelin sheath; These points are called the nodes of Ranvier. Examples of myelinated axons are those in sensory nerve fibers and nerves connected to skeletal muscles. In non-myelinated cells, the nerve impulse is propagated more diffusely.
The nervous system has two divisions: The somatic, which allow voluntary control over skeletal muscle, and the autonomic, which is involuntary and controls cardiac and smooth muscle and glands. The autonomic nervous system has two divisions: The sympathetic and the parasympathetic. Many, but not all, of the muscles and glands that distribute nerve impulses to the larger interior organs possess a double nerve supply; in such cases the two divisions may exert opposing effects. Thus, the sympathetic system increases heartbeat, and the parasympathetic system decreases heartbeat. The two nervous systems are not always antagonistic, however. For example, both nerve supplies to the salivary glands excite the cells of secretion. Furthermore, a single division of the autonomic nervous system may both excite and inhibit a single effector, as in the sympathetic supply to the blood vessels of skeletal muscle. Finally, the sweat glands, the muscles that cause involuntary erection or bristling of the hair, the smooth muscle of the spleen, and the blood vessels of the skin and skeletal muscle are actuated only by the sympathetic division.
Voluntary movement of head, limbs, and body is caused by nerve impulses arising in the motor area of the cortex of the brain and carried by cranial nerves or by nerves that emerge from the spinal cord to connect with skeletal muscles. The reaction involves both excitation of nerve cells stimulating the muscles involved and inhibition of the cells that stimulate opposing muscles. A nerve impulse is an electrical change within a nerve cell or fiber; Measured in millivolts, it lasts a few milliseconds and can be recorded by electrodes.
The human brain has three major structural components: The large dome-shaped cerebrum, the smaller somewhat spherical cerebellum, and the brainstem. Prominent in the brainstem are the medulla oblongata (the egg-shaped enlargement at the center) and the thalamus (between the medulla and the cerebrum). The cerebrum is responsible for intelligence and reasoning. The cerebellum helps to maintain balance and posture. The medulla is involved in maintaining involuntary functions such as respiration, and the thalamus acts as a relay center for electrical impulses traveling to and from the cerebral cortex. Lack of blood flow to any part of the brain results in a stroke, permanent damage that interferes with the functions of the affected part of the brain.
Movement may occur also in direct response to an outside stimulus, thus, a tap on the knee causes a jerk, and a light shone into the eye makes the pupil contract. These involuntary responses are called reflexes. Various nerve terminals called receptors constantly send impulses into the central nervous system. These are of three classes: exteroceptors, which are sensitive to pain, temperature, touch, and pressure; interoceptors, which react to changes in the internal environment; and proprioceptors, which respond to variations in movement, position, and tension. These impulses terminate in special areas of the brain, as do of those special receptors concerned with sight, hearing, smell, and taste.
Whereas most major nerves emerge from the spinal cord, the 12 pairs of cranial nerves project directly from the brain. All but 1 pair relay motor or sensory information (or both); the tenth, or vagus nerve, affects visceral functions such as heart rate, vasoconstriction, and contraction of the smooth muscle found in the walls of the trachea, stomach, and intestine.
Muscular contractions do not always cause actual movement. A small fraction of the total number of fibers in most muscles are usually contracting. This serves to maintain the posture of a limb and enables the limb to resist passive elongation or stretch. This slight continuous contraction is called muscle tone.
In 1946 Axelrod joined the laboratory of American pharmacologist Bernard Brodie at Goldwater Memorial Hospital in New York. The pair conducted research on pain-relieving drugs called analgesics. They identified a pain-relieving chemical known as acetaminophen. This drug was later developed and marketed by the drug company Johnson & Johnson under the brand-name Tylenol.
In 1949 Axelrod took a position at the National Heart Institute, a branch of the National Institutes of Health (NIH). There Axelrod studied how the body processes certain drugs that cause behavioral changes, including amphetamines, ephedrine, and mescaline. He identified a group of enzymes that help these drugs break down in the body. These enzymes, called cytochrome-P450 monoxygenases, have been studied extensively by other scientists, particularly in cancer research.
Realizing that career advancement in the sciences requires a doctoral degree, in 1954 Axelrod took a leave of absence from his job at the National Heart Institute to attend The George Washington University. He earned his doctorate in pharmacology in 1955. That same year he was named chief of pharmacology at the National Institute of Mental Health (NIMH) another branch of NIH.
At NIMH, Joseph Axelrod began research on neurotransmitters. A nerve cell releases a neurotransmitter to spur a neighboring cell into action. In the 1950s most scientists believed that a neurotransmitter became inactive once it stimulated a neighboring cell. But Axelrod’s research found that the neurotransmitter returns to the first nerve cell, in a process known as reuptake, where it is broken down by enzymes or repackaged for reuse. This research led to the creation of a number of drugs that prevent the reuptake process, enabling a neurotransmitter to remain active for a longer period of time.
Axelrod’s research revolutionized the understanding of many mental-health disorders, including depression, anxiety, and schizophrenia. Prior to his research, psychiatry focused on the relationship of life experiences to mental health problems. But Axelrod's research proved that mental-health disorders were often the result of complicated brain chemistry. His research spurred the development of new drugs that advanced the treatment of mental-health conditions. Among these are selective serotonin reuptake inhibitors, including the antidepressants fluoxetine, sold under the brand name Prozac, sertraline(Zoloft) and paroxetine (Paxil).
The study of the biochemistry of memory is another exciting scientific enterprise, but one that can only be touched upon here. Scientists estimate that an adult human brain contains about 100 billion neurons. Each of these is connected to hundreds or thousands of other neurons, forming trillions of neural connections. Neurons communicate by chemical messengers called neurotransmitters. An electrical signal travels along the neuron, triggering the release of neurotransmitters at the synapse, the small gap between neurons. The neurotransmitters travel across the synapse and act on the next neuron by binding with protein molecules called receptors. Most scientists believe that memories are somehow stored among the brain's trillions of synapses, rather than in the neurons themselves.
Scientists who study the biochemistry of learning and memory often focus on the marine snail Aplysia because its simple nervous system allows them to study the effects of various stimuli on specific synapses. A change in the snail's behavior due to learning can be correlated with a change at the level of the synapse. One exciting scientific frontier is discovering the changes in neurotransmitters that occur at the level of the synapse.
Other researchers have implicated glucose, a sugar and insulin(a hormone secreted by the pancreas) as important to learning and memory. Humans and other animals given these substances show an improved capacity to learn and remember. Typically, when animals or humans ingest glucose, the pancreas responds by increasing insulin production, so it is difficult to determine which substance contributes to improved performance. Some studies in humans that have systematically varied the amount of glucose and insulin in the blood have shown that insulin may be the more important of the two substances for learning.
Scientists also have examined the influence of genes on learning and memory. In one study, scientists bred strains of mice with extra copies of a gene that helps build a protein called N-methyl-D-aspartate, or NMDA. This protein acts as a receptor for certain neurotransmitters. The genetically altered mice outperformed normal mice on a variety of tests of learning and memory. In addition, other studies have found that chemically blocking NMDA receptor impairs learning in laboratory rats. Future discoveries from genetic and biochemical studies may lead to treatments for memory deficits from Alzheimer's disease and other conditions that affect memory.
Alzheimer's Disease, progressive brain disorders that causes a gradual and irreversible decline in memory, language skills, perception of time and space, and, eventually, the ability to care for oneself. First described by German psychiatrist Alois Alzheimer in 1906, Alzheimer's disease was initially thought to be a rare condition affecting only young people, and was referred to as prehensile dementia. Today late-onset Alzheimer's disease is recognized as the most common cause of the loss of mental function in those aged 65 and over. Alzheimer's in people in their 30s, 40s, and 50s, called early-onset Alzheimer's disease, occurs less frequently, accountings for less than 10 percent of the estimated 4 million Alzheimer's cases in the United States.
Although Alzheimer's disease is not a normal part of the aging process, the risk of developing the disease increases as people grow older. About 10 percent of the United States population over the age of 65 is affected by Alzheimer's disease, and nearly 50 percent of those over age 85 may have the disease.
Alzheimer's disease takes a devastating toll, not only on the patients, but also on those who love and care for them. Some patients experience immense fear and frustration as they struggle with once commonplace tasks and slowly lose their independence. Family, friends, and especially those who provide daily care suffer immeasurable pain and stress as they witness Alzheimer's disease slowly take their loved one from them.
The onset of Alzheimer's disease is usually very gradual. In the early stages, Alzheimer's patients have relatively mild problems learning new information and remembering where they have left common objects, such as keys or a wallet. In time, they begin to have trouble recollecting recent events and finding the right words to express themselves. As the disease progresses, patients may have difficulty remembering what day or month it is, or finding their way around familiar surroundings. They may develop a tendency to wander off and then be unable to find their way back. Patients often become irritable or withdrawn as they struggle with fear and frustration when once commonplace tasks become unfamiliar and intimidating. Behavioral changes may become more pronounced as patients become paranoid or delusional and unable to engage in normal conversation.
Eventually Alzheimer's patients become completely incapacitated and unable to take care of their most basic life functions, such as eating and using the bathroom. Alzheimer's patients may live many years with the disease, usually dying from other disorders that may develop, such as pneumonia. Typically the time from initial diagnosis until death is seven to ten years, but this is quite variable and can range from three to twenty years, depending on the age of the onset, other medical conditions present, and the care patients receive.
The brains of patients with Alzheimer's have distinctive formations - abnormally shaped proteins called tangles and plaques - that are recognized as the hallmark of the disease. Not all brain regions show these characteristic formations. The areas most prominently affected are those related to memory.
Tangles are long, slender tendrils found inside nerve cells, or neurons. Scientists have learned that when a protein-called tau becomes altered, it may cause the characteristic tangles in the brain of the Alzheimer’s patient. In healthy brains, tau provides structural support for neurons, but in Alzheimer's patients this structural support collapses.
Plaques, or clumps of fibers, form outside the neurons in the adjacent brain tissue. Scientists found that a type of protein, called amyloid precursor protein, forms toxic plaques when it is cut in two places. Researchers have isolated the enzyme beta-secretes, which is believed to make one of the cuts in the amyloid precursor protein. Researchers also identified another enzyme, called gamma secretes, that makes the second cut in the amyloid precursor protein. These two enzymes snip the amyloid precursor protein into fragments that then accumulate to form plaques that are toxic to neurons.
Scientists have found that tangles and plaques cause neurons in the brains of Alzheimer's patients to shrink and eventually die, first in the memory and language centers and finally throughout the brain. This widespread neuron degeneration leaves gaps in the brain's messaging network that may interfere with communication between cells, causing some of the symptoms of Alzheimer’s disease.
Alzheimer's patients have lower levels of neurotransmitters, chemicals that carry complex messages back and forth between the nerve cells. For instance, Alzheimer's disease seems to decrease the level of the neurotransmitter acetylcholine, which is known to influence memory. A deficiency in other neurotransmitters, including somatostatin and corticotropin-releasing factor, and, particularly in younger patients, serotonin and norepinephrine, also interferes with normal communication between brain cells.
The causes of Alzheimer's disease remain a mystery, but researchers have found that particular groups of people have risk factors that make them more likely to develop the disease than the general population. For example, people with a family history of Alzheimer's are more likely to develop Alzheimer's disease.
Some of the most promising Alzheimer's research is being conducted in the field of genetics to learn the role a family history of the disease has in its development. Scientists have learned that people who are carriers of a specific version of the apolipoprotein E gene (apoE genes), found on chromosome 19, are several times more likely to develop Alzheimer's than carriers of other versions of the apoE gene. The most common version of this gene in the general population is apoE3. Nearly half of all late-onset Alzheimer’s patients have the fewer in common apoE4 versions, however, and research has shown that this gene plays a role in Alzheimer's disease. Scientists have also found evidence that variations in one or more genes located on chromosomes 1, 10, and 14 may increase a person’s risk for Alzheimer's disease. Scientists have identified the gene variations on chromosomes 1 and 14 and learned that these genes produce mutations in proteins called presenilins. These mutated proteins apparently trigger the activity of the enzyme gamma secretase, which splices the amyloid precursor protein.
Researchers have made similar strides in the investigation of early-onset Alzheimer's disease. A series of genetic mutations in patients with early-onset Alzheimer's has been linked to the production of amyloid precursor protein, the protein in plaques that may be implicated in the destruction of neurons. One mutation is particularly interesting to geneticists because it occurs on a gene involved in the genetic disorder Down syndrome. People with Down syndrome usually develop plaques and tangles in their brains as they get older, and researchers believe that learning more about the similarities between Down syndrome and Alzheimer's may further our understanding of the genetic elements of the disease.
Some studies suggest that one or more factors other than heredity may determine whether people develop the disease. One study published in February 2001 compared residents of Ibadan, Nigeria, who eat a mostly low-fat vegetarian diet, with African Americans living in Indianapolis, Indiana, whose diet included a variety of high-fat foods. The Nigerians were less likely to develop Alzheimer’s disease compared to their U.S. counterparts. Some researchers suspect that health imposes on high blood pressure, atherosclerosis (arteries clogged by fatty deposits), high cholesterol levels, or other cardiovascular problems may play a role in the development of the disease.
Other studies have suggested that environmental agents may be a possible cause of Alzheimer's disease; for example, one study suggested that high levels of aluminum in the brain may be a risk factor. Several scientists initiated research projects to further investigate this connection, but no conclusive evidence has been found linking aluminum with Alzheimer's disease. Similarly, investigations into other potential environmental causes, such as zinc exposure, viral agents, and food-borne poisons, while initially promising, have generally turned up inconclusive results.
Some studies indicate that brain trauma can trigger a degenerative process that results in Alzheimer's disease. In one study, an analysis of the medical records scribed upon veterans of World War II (1939-1945) linked serious head injury in early adulthood with Alzheimer's disease in later life. The study also looked at other factors that could possibly influence the development of the disease among the veterans, such as the presence of the apoE gene, but no other factors were identified.
Alzheimer’s disease is only positively diagnosed by examining brain tissue under a microscope to see the hallmark plaques and tangles, and this is only possible after a patient dies. As a result, physicians rely on a series of other techniques to diagnose probable Alzheimer's disease in living patients. Diagnosis begins by ruling out other problems that cause memory loss, such as stroke, depression, alcoholism, and the use of certain prescription drugs. The patient undergoes a thorough examination, including specialized brain scans, to eliminate other disorders. The patient may be given a detailed evaluation called a neuropsychological examination, which is designed to evaluate a patient’s ability to perform specific mental tasks. This helps the physician determine whether the patient is showing the characteristic symptoms of Alzheimer's disease - progressively worsening memory problems, language difficulties, and trouble with spatial direction and time. The physician also asks about the patient's family medical history to learn about any past serious illnesses, which may give a hint about the patient's current symptoms.
Evidence shows that there is inflammation in the brains of Alzheimer's patients, which may be associated with the production of amyloid precursor protein. Studies are underway to find drugs that prevent this inflammation, to possibly slow or even halt the progress of the disease. Other promising approaches center on mechanisms that manipulate amyloid precursor protein production or accumulation. Drugs are in development that may block the activity of the enzymes that cut the amyloid precursor protein, halting amyloid production. Other studies in mice suggest those vaccinating animals with amyloid precursor protein can produce a reaction that clears amyloid precursor protein from the brain. Physicians have started vaccination studies in humans to determine if the same potentially beneficial effects can be obtained. There is still much to be learned, but as scientists better understand the genetic components of Alzheimer’s, the roles of the amyloid precursor protein and the tau protein in the disease, and the mechanisms of nerve cell degeneration, the possibility that a treatment will be developed is more likely.
The responsibility for caring for Alzheimer's patients generally falls on their spouses and children. Care givers must constantly be on guard for the possibility of Alzheimer's patients wandering away or becoming agitated or confused in a manner that jeopardizes the patient or others. Coping with a loved one's decline and inability to recognize familiar face causes enormous pain.
The increased burden faced by families is intense, and the life of the Alzheimer's care giver is often called a 36-hour day. Not surprisingly, care givers often develop health and psychological problems of their own as a result of this stress. The Alzheimer's Association, a national organization with local chapters throughout the United States, was formed in 1980 in large measure to provide support for Alzheimer's care givers. Today, national and local chapters are a valuable source for information, referral, and advice.
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