A highly organized collection of cells known as nerve cells, or neurons, constitutes the nervous system, which is found in all higher forms of animal life. These nerve cells collect information from the environment by means of receptors. They coordinate the information with the internal activities of the organism in a process known as integration. They also store information in terms of memory and generate adaptive patterns of behavior. Nervous systems vary greatly in form and complexity. They range from the simple nerve nets of such coelenterates as jellyfish to the elaborate, segmentally organized, and bilaterally symmetrical structures of higher invertebrates and most vertebrate species.
The nervous system of higher organisms such as human beings is divided into a central system that comprises the Brain and Spinal Cord, and a peripheral system that comprises the remaining nervous tissue. The central nervous system coordinates the activity of the system as a whole. The motor nervous system innervates skeletal muscle, skin, and joints and controls voluntary actions, whereas the autonomic nervous system coordinates mainly involuntary actions such as heartbeat.
The basic building block of a nervous system is the neuron, or nerve cell, a cell that is specialized for the transmission of information into, within, and out of the animal. The human brain alone has about one trillion individual nerve cells, any one of which may have several thousand direct connections to other nerve cells in the system.
Structure and Function
A neuron of the human brain has three main regions: the cell body (soma), the dendrites, and the axon. The cell body, which ranges in size from 2 to 500 micra (or microns) in diameter. It contains the basic constituents of most animal CELLS--a nucleus, which has a nucleolus and chromosomes; and such cytoplasmic bodies as ribosomes, mitochondria, and endoplasmic reticulum. The dendrites are branched structures that have cytoplasmic continuity with the cell body. They function to receive signals from other nerve cells. The axon is a long fiber--up to 9 m (30 ft) in some whales--that is relatively uniform in diameter and often is covered with a myelin sheath. It normally serves to transmit information from one neuron to adjacent neurons.
Neurons of many animals also contain specialized structures that serve diverse functions. Nissl bodies contain ribonucleoproteins and are especially involved in protein synthesis. Fibrillar structures have neurofilaments and microtubules and appear to participate in the transport of various substances throughout the neuron. Synaptic bulbs, often located at the ends of axons, are clear swellings that contain round, flattened vesicles and seem to be involved with the transmission of impulses.
A neuron usually is considered multipolar, referring to the many processes emanating from the soma, and heteropolar, because these processes are anatomically distinct (axons and dendrites). Multipolar-heteropolar neurons are the dominant class of neural cells in the vertebrate central nervous system. Most sensory neurons are bipolar and are found in the peripheral nervous system. In higher invertebrates, such as insects, neurons with a single process connected to the soma most commonly function both as interneurons and motor neurons. These nerve cells are classified as unipolar.
When the processes of a neuron cannot be readily distinguished on anatomical grounds, the neuron is called isopolar. Isopolar neurons appear to be the most primitive nerve cells; they commonly occur, for example, in the nerve nets of coelenterates (jellyfish and hydra). Higher vertebrates also contain some isopolar nerve cells, such as the amacrine cells of the human retina. It is likely that all of these types of neurons developed from EPITHELIUM cells (cells of skin and organ membranes), which exhibit a limited capacity for excitation and conduction.
Receptors are neurons that bring information into the nervous system. Classically, sensory reception has been divided into the five senses of hearing, vision, touch, taste, and smell. Today receptors are more commonly classified in terms of the physical forms of stimulation that excite them: chemoreception, electroreception, mechanoreception, photoreception, and thermoreception. Nociceptors are stimulated by damage to tissues.
In spite of their physical diversity, most nerve cells operate in a similar way--they generate and carry two basic types of electrochemical signals known as graded potentials and spike discharges (see NEUROPHYSIOLOGY). Because of the unequal distribution of some ions across the nerve-cell membrane, an inactive nerve cell has what is known as a resting potential, with the inside of the cell having a negative charge with respect to the outside of the cell. When the neuron is depolarized, this potential difference between inside and outside is reduced, and the nerve cell propagates an impulse to the end of the fiber. The graded-potential change, caused by depolarization of the dendrites, moves along the branches toward the soma.
If the total depolarization is great enough, one or more spike discharges can be generated at the base of the axon and carried toward the synaptic terminal. In spikes, the frequency of discharges codes for the intensity of the signal. When these spikes reach synaptic bulbs, they induce the release of special chemical transmitters that have been stored in vesicles and can give rise to graded, postsynaptic potentials in the dendrites or soma of the next neuron.
A neuron becomes hyperpolarized when its resting potential increases, causing the neuron to be less likely to carry messages. The neuron, as a result, becomes inhibited rather than excited. Certain transmitters are excitatory, stimulating nerve-impulse propagation, and others are inhibitory, causing hyperpolarization to occur.
Structure and Function
The axons of many vertebrate neurons are covered with a myelin sheath, which acts like insulation on a wire and greatly extends the efficiency of the conduction of spike discharges. This insulating sheath is made of glial cells. In the vertebrate central nervous system, glial cells are distinguished as oligodendroglia, and in the peripheral nervous system they are called Schwann cells. True myelin sheaths are not found in invertebrates, although similar coverings do exist in fast-conducting giant fiber systems of earthworms and shrimps. Myelin sheaths promote speed and reliability of nerve-impulse conduction. The 12 micron myelinated axon of a frog can conduct a signal as rapidly as the 350 micron axon of a squid. The one million myelinated axons in a mammalian optic nerve, which is 2 mm in diameter, would need an estimated diameter of nearly 50 mm to function at the same efficiency if they did not have a myelin sheath.
Nodes of Ranvier
Myelinated fibers have small gaps, called nodes of Ranvier, between successive glial cells; the action potentials between them jump in a process called saltatory conduction. Humans with myelin deficiency, such as those afflicted with multiple sclerosis, can experience serious difficulties in nervous system functioning because of decreased speeds and reliability of conduction.
The points of closest affinity and functional connection between neurons are known as synapses. Actually, most neurons do not signal each other by direct anatomical contact; they are normally separated by a small synaptic cleft of approximately 200 angstroms (one angstrom equals one hundred-millionth of a centimeter). NEUROTRANSMITTERS--chemical substances that effect impulses--are released into the synaptic cleft from the presynaptic terminals. They are received by the postsynaptic membrane of the receiving neuron. Occasionally, tight junctions exist, in which the transmission of information from one neuron to the next is primarily electrical, not chemical. Most common synapses occur between the axon of the sender cell and the dendrites or soma of the receiver cell. Synapses between two axons, dendrites, or soma are also known to occur. The particular synaptic location between adjacent cells can affect the types of signals that are transmitted. Also, in higher animals the synapses carry information primarily in one direction only, greatly enhancing the sophistication of neural codes.
A vertebrate spinal cord in cross-section resembles a gray butterfly--the gray matter with cell bodies and associated synapses is arranged within a white oval, which contains the incoming (afferent) and outgoing (efferent) axons. In each segment sensory afferent fibers are concentrated into dorsal roots that are connected to associated ganglia outside of the spinal cord. Efferent fibers are concentrated in the ventral roots. The spinal cord's cervical, thoracic, lumbar, and sacral regions, control incoming, integrative, and outgoing nervous functions for successive body parts.
The spinal cord also houses and protects the two main branches of the Autonomic Nervous System, which controls involuntary, unconscious actions of smooth muscle and glands. These two branches are the sympathetic and parasympathetic systems. The thoracic and lumbar segments of the spinal cord contain nerves of the sympathetic system. The sympathetic system serves an adrenergic function, mobilizing the organism in a "fight or flight" reaction in emergencies. The parasympathetic system, located in cranial and sacral segments, is primarily cholinergic in function, serving to relax the organism.
The Brain connects with the spinal cord at the medulla, or myelencephalon, the site of the more primitive regulatory functions. Great fiber tracts between the brain and spinal cord cross in the medulla. The entrance and exit points of 12 cranial nerves, which serve a variety of somatic and visceral functions, are located in the medulla as well as in the next higher level of the brain, the pons.
Metencephalon, Cerebellum, and Mesencephalon
The pons (the metencephalon) and the cerebellum are responsible for many basic tasks of sensory and motor coordination. The next level of the brain, the mesencephalon (midbrain), is involved with still more complex functions of sensory-motor processing. The brain stem (medulla, pons, and midbrain) houses the reticular formation, a complex structure that combines many otherwise separate sensory and motor functions. The reticular formation also influences generalized levels of consciousness, including cycles of waking and sleeping.
The diencephalon contains complex integrative structures, including the thalamus, which coordinates multiple sensory signals, and the hypothalamus, which plays a critical role in motivated behaviors, such as feeding, drinking, mating, and fighting. The hypothalamus is a major site of neurosecretion, connecting the nervous system to the endocrine (hormone) system by means of the pituitary.
The telencephalon, largely the cerebrum, is the apex of sophisticated brain structure and undoubtedly plays a major role in the more subtle emotional, coordinative, and intellectual functions. The cerebral cortex, the highly complex outer portion, is divided into three major zones: the archipallium, the paleopallium, and the neopallium. It is at the cortical level that the most-striking features of precise nervous-system organization are represented. For example, in the motor cortex as well as the somatosensory ("body" sensory) cortex of mammals, various body segments are anatomically localized in proportion to their relative importance. These regions are even further specialized; for example, in the somatosensory cortex, specific columns of cells provide awareness of joint movement, light touch, or deflection of body hair. Similarly, cortical regions are present for the processing of auditory, visual, olfactory, and other such stimuli. In the visual cortex, columns of cells respond specifically to visual inputs that have certain orientations.
The precision and intricacy of nervous system architecture is well illustrated in the mammalian cerebellum, a large structure at the back of the head that plays an important role in various forms of sensory-motor coordination. Five types of neuron--Purkinje, Golgi, stellate, basket, and granule cells--are located here and are distributed in precise relationship to one another, permitting excitation and inhibition for the control of a variety of skilled tasks. A similar ordered complexity is evident among the five cell types of the vertebrate retina--photoreceptor, horizontal, bipolar, amacrine, and retinal ganglion cells. The highly ordered interactions among these cells process the rich details of the visual environment. Similarly impressive specializations are found in other receptors and central nervous system structures throughout all higher forms of animal life.
When a neuron is stimulated, an all or none responce occurs. An impulse is either generated or itís not. If the impulse is generated a sudden change occurs in the permeability of the mebrane at the point of stimulation. The mebrane becomes permeable to Na+ ions, which then diffuse rapidly from the outside to the inside of the membrane. As a result the inner surface of the membrane becomes more positively charged than the outer surface. This reversal of resting-state electrical potential is called depolarization. At first the depolarization occurs only a short segment of the membrane but it immediatly disrupts the adjacent part of the membrane, which then becomes depolarized. A wave of depolarization called action potential moves along the membrane. The action potential is the impulse.
The presence of the myelim sheath, a structure found primarily in vertebrates, affects the speed of the impulse. Electrical stimulation cannot take place through the myelin sheath. Therefore the impulse moves down the axon until it reaches one of the nodes of Ranvier. Here depolarization occurs very quickly and creates a new action potential, which jumps across the gap of the myelin sheath to the next section with little loss of energy. At each gap the energy of the original stimulus is regenerated providing a constant, strong stimulus along the lenght of the axon.
The frequency at which impulses travel along the axon is limited in part by the refractory period, the time that follows the passage of a nerve impulse. During the refractory period the neuron is returning to its resting potential and cannot be stimulated. The period of time in which a neuron will not accept an impulse is about 0.0004 of a second.
When a nerve impulse travels along the lenght of an axon, it eventually reaches the axon terminals. The axon terminals lie near an organ, a gland, or the dendrite of another neuron, but do not touch it. The small space between the axon and the next neuron is called the synapse.
Impulses are carried across a synapse by chemical messangers called neurotransmitters. These chemicals are stored in synaptic vesicles embetted in a bouton, boulblike structure at th tip of an axon terminal. The bouton is enclosed by a presynaptic membrane which lies almost adjecent to to the postsynaptic membrane.
When an impulse reaches the axon terminal, the synaptic vesicles fuse with the presynaptic membrane and release neurotransmiters into the gap. After their contents are released, the vesicles ussulally pull away from the membrane and return to the cytoplasm, where they once again are filled with neurotransmitters.
Neurotransmitters travel across the gap and bind to receptor molecules in the postsynaptic membrane. The interaction of the neurotransmitter snd the receptor creates an action potential that then travels down the receiving dendrite to the cell body.
In the synapse neurotransmitters are destroyed by the action of enzymes. It is important for the neurotransmitters to be destroyed so that they will not continue to stimulate the receiving neuron.
Impulses are transmitted along neurons until they reach a muscle. In the muscle the impulse causes the muscle to contract. When anyones finger is pricked, this causes it to contract.
One of the more interesting and important features of the spinal cord is that even when it is separated from the brain, it can control fundamental integrative functions known as reflexes. A REFLEX can be considered schematically in terms of a sensory (receptor or afferent) cell that excites an interneuron, which in turn excites a motor (efferent) neuron. A variable lapse between the stimulus and the response reflects the time necessary to process the signal carried by the reflex afferent nerves. The strength of the response corresponds to a summation through time as well as over the different pathways. The response to a standard signal may take some time to develop fully. After the signal is removed the response may continue for a certain period of time. Different reflexes within the system interact with each other in complex patterns of mutual excitation and inhibition.
Perhaps the most interesting feature derived from studies of nervous system reflexes is the highly intimate and intricate connection between sensory inputs and motor outputs. The general principle of FEEDBACK control appears to be important for complex nervous-system functions. Mammalian muscle fibers, for example, contain specialized sensory cells (spindle organs) that convey to the spinal cord information concerning their current state of contraction. The output to these muscles from both the spinal cord and the brain depends, in part, upon the signals from spindle fibers. Further, the brain can send special signals by way of the efferent system, which selectively changes the bias of these muscle spindles and affects the responsiveness of the muscle to signals of the motor neurons. Thus, sensory signals affect motor responses, which in turn affect sensory signals.
Operation of Neurons
At least four distinguishable classes of operation exist for the vertebrate nervous system. First, sensory inputs can generate the specific details of motor response, a direct transfer process. More commonly, the details of sensory input depend upon the integration of afferent nerve stimulation as well as the current state of responsiveness of interneurons and motor neurons. Afferent signals can also serve to trigger responses, the characteristics of which are basically inherent to the structure stimulated. Finally, integrative and motor cells can fire spontaneously, even in the absence of sensory input. In each case, the vertebrate spinal cord normally acts in cooperation with the brain.
Diseases of the nervous system comprise an assortment of afflictions that vary in terms of cause, areas of the nervous system involved, and disturbances of function. All levels of the BRAIN, SPINAL CORD, and peripheral nervous system can be affected. Manifestations of such diseases include diminished muscular strength with or without wasting, altered sensation, incoordination, and impaired bowel, bladder, or sexual functions. Disturbances in the regulation of heart rate, blood pressure, and respiration may occur. Movements may be diminished, abnormally increased, or involuntary.
Disorders of the cerebral hemispheres are characterized by seizures, decrease in intellectual functioning, confusion, disorientation, and profound derangements either in comprehension or in speaking or writing . Cerebral-hemisphere anomalies include gross underdevelopment, abnormal cortical convolutions (gyri), and their assorted malfunctions resulting in intellectual impairment or decreased life expectancy. Hydrocephaly, caused by a disturbance of cerebrospinal fluid circulation or absorption in the cranial cavity, results in enlargement of the brain ventricles, thinning of the cerebral mantle, and Mental retardation.
Congenital and Developmental Diseases
Congenital or developmental disorders (see BIRTH DEFECTS), which occur in a small percentage of births, include almost every imaginable anomaly of structure and function. For example, SPINA BIFIDA involves the incomplete closure of the embryonic neural tube, resulting in an incomplete vertebral column roof. The spinal cord and its meningeal investments and roots may extrude through bony clefts, causing paralysis of the lower extremities, bowel, and bladder. An infection, such as MENINGITIS, can occur early in life, resulting in severe neurological impairment and, possibly, death. SYRINGOMYELIA, a progressive formation of a cavity in the spinal cord, is characterized by loss of perception of pain and temperature and later by weakness and wasting of the muscles. Maldevelopment of blood-vessel walls in the brain may underlie later development of aneurysms or vascular tumors, both of which may be responsible for cerebral hemorrhage.
Cerebral palsy, affecting about 2 newborns in 1,000, denotes a broad group of developmental disorders resulting from a defect in the developing fetal brain. It may be caused by such factors as infection, blood disorders, metabolic deficiencies, anoxia, or trauma. An increasingly recognized number of hereditary errors of metabolism--for example, Phenylketonuria--cause specific enzyme deficiencies that result in abnormal accumulations of injurious chemical substances. These excess chemical deposits often underlie mental retardation. One of the many significant mental-deficiency syndromes is mongolism, or Down's syndrome, resulting from a chromosomal abnormality that occurs at the time of fertilization.
Degenerative diseases commonly have dissimilar or unrelated pathologies. Frequently, the causes of these types of disorders are unknown. Alzheimer's and Pick's diseases, so-called presenile dementias, are characterized by unremitting loss of cortical neurons with resultant cerebral atrophy. Loss of intellectual function , behavioral and personality changes, language and perceptual deficits, seizures, and disturbances of movement are common.
Parkinson's disease is a degenerative disorder that affects half a million people in the United States annually. It involves the central gray matter of the brain (basal ganglia), resulting in deficiency of a neurotransmitter known as dopamine. The common form of this disease is caused by a premature degeneration of certain basal nuclei. Many people infected by Encephalitis during the 1919-26 pandemic contracted a form of Parkinson's disease afterwards. Many centrally acting psychotropic drugs, manganese, other toxins, and anoxic cerebral damage may produce parkinsonian syndromes. Symptoms include decreased spontaneous movement, increased muscle tone (rigidity), and rhythmic tremor at rest.
Multiple sclerosis is an important disease, with an annual U.S. incidence of 5 to 30 per 100,000 population, depending upon geographic areas. It is characterized by circumscribed, often small areas of degeneration of myelinated nerve fibers. Eventually the nerve fiber (axon) loses the ability to function properly. These plaques become increasingly numerous, resulting in widespread neural disconnections. Symptoms include incoordination, weakness, disturbances of vision, and numbness. Those residing in temperate climates have a higher incidence of this disorder. Its progress may be punctuated by long symptom-free periods.
Motor-neuron disease, such as amyotrophic lateral sclerosis, is characterized by a rapid loss of cells within the areas of the brain and spinal cord responsible for the initiation of movement. Muscular weakness and degeneration with eventual paralysis ensue. Progressive muscular atrophy is a form of this disorder in which primarily the motor cells of the spinal cord are affected. Muscular dystrophy differs from motor-neuron disease in that the degeneration is restricted to the muscle itself and is usually transmitted genetically.
Huntington's chorea is an inherited disorder that affects primarily the adult. Dementia, behavioral changes, and abnormal, jerky movements (chorea) are its major features, reflecting changes in the cerebral cortex and the basal nuclei. Hereditary spinal ataxias are disorders primarily affecting children and young adults. They are characterized by clumsy gait, incoordination, and muscular weakness.
Wilson's disease is a genetic disturbance affecting copper metabolism. Excess copper deposits result in cerebral changes, impaired coordination (ataxia), tremors, and liver failure.
Practically all conceivable infectious organisms (bacteria, fungi, viruses, yeasts, and protozoa) have been known to infect the nervous system. Certain organisms, for example, pneumococci, are common invaders, whereas others are rare. Invasion may be by direct entry through penetrating wounds or by spreading throughout the circulatory system. The infection may be severe or relatively mild, depending on the particular pathogen and the immune response of the host. Meningitis denotes invasion of the meningeal covering of the brain, spinal cord, and accessory blood vessels; encephalitis implies infection of the brain only; meningoencephalitis, which combines aspects of both disorders, commonly occurs. An abscess of the brain or spinal cord is a localized cavity that contains pus surrounded by a wall of inflammatory cells and scar tissue. Several diseases are currently under investigation, including kuru and Creutzfeldt-Jakob disease. The infective agents of these two disorders differ significantly from known viruses--they are capable of replication, are resistant to conventional sterilization, and have distinctive chemical characteristics. Infective agents of this type may possibly be implicated in other neurological diseases of as yet unknown cause.
The nervous system has high energy requirements and is imbued with an elaborate vascular bed and a rich blood supply. It is sensitive to impaired circulation or deficits in oxygen or glucose supply. STROKE is a result of localized circulatory impairment. It may result from occlusion of a major artery, or less commonly, of a vein, that supplies a certain area of the brain, brain stem, or spinal cord. Stroke victims suffer from irreversible loss of brain function due to tissue damage. The obstruction to normal blood flow may occur because of hardening of the vessel wall (arteriosclerosis) or blood-clot formation (thrombus). A clot can become dislodged in one part of the circulatory system and travel to the brain, causing an obstruction known as an embolism. Hemorrhagic stroke principally occurs in patients afflicted with long-standing high blood pressure. In this case blood escapes under pressure from a damaged artery and intrudes massively upon the brain, destroying tissue. In addition hemorrhage may result from a rupture of an aneurysm, from a vascular anomaly, or because of a disturbance in clotting mechanisms.
TUMORS of the nervous system can either arise within the brain or spinal cord or can occur in other body tissues and then spread (by a process known as metastasis) to the nervous system. Gliomas constitute an important group of malignant tumors that appear to arise from the microscopic supportive tissue of the nervous system known as glia. Gliomas comprise 40 to 45 percent of all nervous system tumors. Meningiomas and neuromas stem from the supportive investments of the brain and spinal cord and are generally nonmalignant. A variety of other primary tumors are recognized; they are named according to the tissue of origin, for example, pituitary tumors and vascular tumors. Metastatic tumors ordinarily are malignant but differ in tissue type depending on the site of origin. Representatives of this group are pulmonary, breast, and melanomatous skin CANCER.
Epilepsy affects somewhat less then 2 percent of the population. It is a periodic, paroxysmal disorder involving cerebral excitability. Symptoms are an alteration of consciousness often associated with excessive motor activity or disturbed sensory perception. During and between attacks abnormal electrical activity of the cerebral cortex can be detected by means of the electroencephalogram. Seizures are regarded as a symptom and not a disease. They result from a great variety of factors that alter cortical excitability; the clinical characteristics of individual attacks, however, tend to be stereotyped and remarkably similar from person to person.
Systemic metabolic disturbances produce wide-ranging effects on the nervous system, as exemplified by stupor or coma seen in liver disease, renal failure, and diabetes. Altered levels of calcium in the blood may produce convulsions. A type of periodic muscular paralysis relates to altered blood potassium levels.
Toxic disorders include botulism, a type of food poisoning that causes muscular paralysis. Cerebral or peripheral nerve disease can be a result of lead, mercury, or arsenic poisoning. Ethyl alcohol, when abused, is a toxin of enormous social and economic importance. Its long-term effects often are difficult to separate from accompanying nutritional deficiency. Alcoholics are subject to seizures and peripheral nerve, brain stem, cerebellar, cerebral, and optic nerve degeneration (see ALCOHOL CONSUMPTION; ALCOHOLISM). Methyl alcohol poisoning produces blindness by its direct effect on the optic nerve.
Injuries can affect the nervous system at any level. In lumbar intervertebral disk disease the spinal nerve roots compress, producing pain, numbness, and weakness of the lower extremity. Spinal-cord damage from vertebral column fracture can cause paraplegia, paralysis of the lower extremities, or quadriplegia, paralysis from the neck down. Injuries to the BRAIN may result in seizures and intellectual, motor, sensory, visual, and language impairment. Accumulations over the brain of blood from torn intracranial vessels may cause death if not surgically relieved.
A less serious, but still debilitating injury common to musicians and computer operators is carpal tunnel syndrome. Tendons in the carpal tunnel, a bone structure in the wrist, swell and prevent circulation to the thumb and first three fingers, causing numbness and sometimes pain. The problem is often caused by repetitive hand and wrist movements.
Diagnosis of neurological disease depends on the careful analysis of symptoms of the illness followed by a thorough examination of the patient. Computerized axial tomography, one of the many valuable diagnostic procedures, allows X-ray visualization of intracranial structures with greater clarity than formerly possible and entails little risk or discomfort to the patient. Recent diagnostic and investigative advances include magnetic resonance imaging, positron emission tomography, and angiographic digital subtraction.