NERVOUS SYSTEM, HUMAN

system that conducts stimuli from sensory receptors to the brain and spinal cord and that conducts impulses back to other parts of the body. As with other higher vertebrates, the human nervous system has two main parts: the central nervous system (the brain and spinal cord) and the peripheral nervous system (the nerves that carry impulses to and from the central nervous system). In humans the brain is especially large and well developed. Additional reading Anatomy of the human nervous system General overviews are provided by Jay B. Angevine, Jr. and Carl W. Cotman, Principles of Neuroanatomy (1981), a short, concise description of anatomical and functional concepts; A. Brodal, Neurological Anatomy in Relation to Clinical Medicine, 3rd ed. (1981), a scholarly source of detailed anatomical information, beautifully presented; Malcolm B. Carpenter, Core Text of Neuroanatomy, 4th ed. (1991), a popular medical-student text with excellent drawings, photographs, and teaching diagrams; Malcolm B. Carpenter and Jerome Sutin, Human Neuroanatomy, 8th ed. (1983), a complete, well-documented source book with coloured atlas; and a work that contributes greatly to three-dimensional concepts, Frank H. Netter (comp.), The Ciba Collection of Medical Illustrations, vol. 1, Nervous System, new ed. (1983), a superb collection of instructive, authoritative colour drawings of the central, peripheral, and autonomic nervous systems as well as diseases of the brain and spinal cord.The development of the human nervous system is discussed by Rita Levi-Montalcini, The Nerve Growth Factor 35 Years Later, Science, 237(4819):11541162 (Sept. 4, 1987), an interesting review of studies of the nerve growth factor by a Nobel Laureate; Keith L. Moore, The Developing Human: Clinically Oriented Embryology, 4th ed. (1988), a popular standard book presenting a synopsis of the embryonic development of the nervous system along with relevant clinical information and congenital malformations; Charles R. Noback, Norman L. Strominger, and Robert J. Demarest, The Human Nervous System: Introduction and Review, 4th ed. (1991), a general account of the development of the nervous system from its inception through old age, augmented with clinically significant information and appropriate illustrations; and Jan Langman, Langman's Medical Embryology, 6th ed. by T.W. Sadler (1990), a well-known work on human embryology with concise text, excellent illustrations and charts, and numerous points of clinical significance.Explorations of the central nervous system include Stephen J. DeArmond, Madeline M. Fusco, and Maynard M. Dewey, Structure of the Human Brain, 3rd ed. (1989), a photographic atlas of brain sections; Duane E. Haines, Neuroanatomy: An Atlas of Structures, Sections, and Systems, 3rd ed. (1991), an atlas of brain photographs and vascular supply, with teaching diagrams; and R. Nieuwenhuys, J. Voogd, and Chr. van Huijzen, The Human Central Nervous System: A Synopsis and Atlas, 2nd rev. ed. (1981), a well-illustrated, readable text.Descriptions of the peripheral nervous systemthe spinal and cranial nervesare included in the work by Haines and in the general overviews cited above; and in a standard anatomy reference work available in 2 editions: Henry Gray, Anatomy of the Human Body, 30th American ed. edited by Carmine D. Clemente (1985), and Gray's Anatomy, 37th British ed. edited by Peter L. Williams et al. (1989).The anatomy of the autonomic nervous system is dealt with in D.J. Cunningham, Cunningham's Textbook of Anatomy, 12th ed. edited by G.J. Romanes (1981), a complete description; and in Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed. by Joel G. Hardman and Lee E. Limbird (1996), a summary of neurotransmission in the autonomic nervous system. Charles R. Noback Duane E. Haines Arthur D. Loewy The Editors of the Encyclopdia Britannica Functions of the human nervous system General summaries are provided by David Jensen, The Human Nervous System (1980); and Peter Nathan, The Nervous System, 3rd ed. (1988), a complete account of the anatomy, physiology, and psychology of the nervous system of humans and other animals, written for readers without an extensive background in biology. Information on sensory receptors can be found in Wilfred M. Copenhaver, Douglas E. Kelly, and Richard L. Wood, Bailey's Textbook of Histology, 17th ed. (1978); Arthur C. Guyton, Basic Human Neurophysiology, 3rd ed. (1981), an account of functional aspects of sensory receptors; and Don W. Fawcett, A Textbook of Histology, 11th ed. (1986). G.H. Parker, The Elementary Nervous System (1919), is a classic book on the origin of the basic receptor-adjustor-effector system of neural function. Charles S. Sherrington, The Integrative Action of the Nervous System, 2nd ed. (1948, reprinted 1973), is a classic on the physiology of reflex mechanisms, by one of the important workers on the subject.Discussions on the regulation of muscular contraction include Bernard Katz, Nerve, Muscle, and Synapse (1966), a clearly written work; Peter B.C. Matthews, Mammalian Muscle Receptors and Their Central Actions (1972), a wide-ranging work dealing with the subject historically, and an article updating this, Evolving Views on the Internal Operation and Functional Role of the Muscle Spindle, The Journal of Physiology, 320:130 (1981); and I.A. Boyd and M.H. Gladden (eds.), The Muscle Spindle (1985), an account of a specialized symposium with brief review articles interspersed.The vestibular system and its functions are the subject of Victor J. Wilson and Geoffrey Melvil Jones, Mammalian Vestibular Physiology (1979), an account of the mammalian vestibular system, including anatomy, biophysics, and physiology, that assumes some physiological knowledge; Robert W. Baloh and Vincente Honrubia, Clinical Neurophysiology of the Vestibular System, 2nd ed. (1990), a review of the vestibular system in relation to disease states; and Peter Rudge, Clinical Neuro-Otology (1983), which outlines from a clinical point of view the vestibular system and which deals with anatomy, physiology, and clinical conditions affecting this system, including an account of the auditory pathways.Discussions of various aspects of the autonomic nervous system include R.F. Schmidt and G. Thews (eds.), Human Physiology, 2nd rev. ed. (1989; originally published in German, 23rd ed., 1987), which contains a general account of the basic physiology of the autonomic nervous system; Arthur D. Loewy and K. Michael Spyer (eds.), Central Regulation of Autonomic Functions (1990), a review of the brain mechanisms involved in regulating the autonomic nervous system; Leonard R. Johnson (ed.), Physiology of the Gastrointestinal Tract, 2nd ed., 2 vol. (1987), a series of comprehensive reviews on the tract's anatomy, physiology, and pathophysiology; and Jan M. Lundberg and Tomas Hkfelt, Multiple Co-existence of Peptides and Classical Transmitters in Peripheral Autonomic and Sensory NeuronsFunctional and Pharmacological Implications, Progress in Brain Research, 68:241262 (1986), a discussion of the role neuropeptides play in neurotransmission in the autonomic nervous system.The following works deal with other functions of the human nervous system: on pain, Ronald Melzack, The Puzzle of Pain (1973); on vision, Richard L. Gregory, Eye and Brain: The Psychology of Seeing, 4th ed. (1990); and on emotion and behaviour, Lloyd S. Woodburne, The Neural Basis of Behavior (1967), a useful review of the anatomy and physiology of the nervous system for the beginning student in biology, medicine, or psychology. See also Richard L. Gregory and O.L. Zangwill (eds.), The Oxford Companion to the Mind (1987).Cerebral functions are described in Aleksandr Romanovich Luria, Higher Cortical Functions in Man, 2nd ed. rev. and expanded (1980; originally published in Russian, 1962); Alan Baddeley, Your Memory: A User's Guide (1982); Ennio de Renzi, Disorders of Space Exploration and Cognition (1982); Andrew W. Ellis, Normality and Pathology in Cognitive Function (1982); Muriel Deutsch Lezak, Neuropsychological Assessment, 2nd ed. (1983); Kenneth M. Heilman and Edward Valenstein, Clinical Neuropsychology, 2nd ed. (1985); Bryan Kolb and Ian Q. Whishaw, Fundamentals of Human Neuropsychology, 3rd ed. (1990); Sally P. Springer and Georg Deutsch, Left Brain, Right Brain, 3rd ed. (1989); and Kevin Walsh, Neuropsychology: A Clinical Approach , 2nd ed. (1987). I.P. Pavlov, Conditioned Reflexes: An Investigation of the Physiological Activity of the Cerebral Cortex (1927, reprinted 1960; originally published in Russian, 1923), describes the classic experiments and studies of cerebral function in response to signals and reflex behaviour as carried out in dogs and their application to humans. Thomas L. Lentz Charles R. Noback Peter W. Nathan Peter B.C. Matthews Peter Rudge Arthur D. Loewy Peter W. Nathan Graham Ratcliff Anatomy of the human nervous system The autonomic nervous system The autonomic nervous system is a part of the peripheral nervous system that functions to regulate the basic visceral processes needed for the maintenance of normal bodily functions. It operates independently of voluntary control, although certain events, such as emotional stress, fear, sexual excitement, and alterations in the sleep-wakefulness cycle, change the level of autonomic activity. The autonomic system is usually defined as a motor system that innervates three major types of tissue: cardiac muscle, smooth muscle, and glands. However, this definition needs to be expanded to encompass the fact that it also relays visceral sensory information into the central nervous system and processes it in such a way as to make alterations in the activity of specific autonomic motor outflows, such as those that control the heart, blood vessels, and other visceral organs. It also causes the release of certain hormones involved in energy metabolism (e.g., insulin, glucagon, epinephrine) or cardiovascular functions (e.g., renin, vasopressin). These integrated responses maintain the normal internal environment of the body in an equilibrium state called homeostasis. The autonomic system consists of two major divisions: the sympathetic nervous system and the parasympathetic nervous system. These often function in antagonistic ways. The motor outflow of both systems is formed by two serially connected sets of neurons. The first set, called preganglionic neurons, originates in the brain stem or the spinal cord, and the second set, called ganglion cells or postganglionic neurons, lies outside the central nervous system in collections of nerve cells called autonomic ganglia. Parasympathetic ganglia tend to lie close to or within the organs or tissues that their neurons innervate, whereas sympathetic ganglia lie at a more distant site from their target organs. Both systems have associated sensory fibres that send feedback information into the central nervous system regarding the functional condition of target tissues. A third division of the autonomic system, termed the enteric nervous system, consists of a collection of neurons embedded within the wall of the entire gastrointestinal tract and its derivatives. This system controls gastrointestinal motility and secretions. Sympathetic nervous system Sympathetic preganglionic neurons originate in the lateral horns of the 12 thoracic and the first 2 or 3 lumbar segments of the spinal cord. (For this reason the sympathetic system is sometimes referred to as the thoracolumbar outflow.) The axons of these neurons exit the spinal cord in the ventral roots and then synapse on either sympathetic ganglion cells or specialized cells in the adrenal gland called chromaffin cells. Anatomy of the human nervous system The peripheral nervous system The peripheral nervous system is a channel for the relay of sensory and motor impulses between the central nervous system on the one hand and the body surface, skeletal muscles, and internal organs on the other hand. It is composed of (1) spinal nerves, (2) cranial nerves, and (3) certain parts of the autonomic nervous system. As in the central nervous system, peripheral nervous pathways are made up of neurons (that is, nerve cell bodies and their axons and dendrites) as well as the points at which one neuron communicates with the next (that is, the synapse). The structures commonly known as nerves (or by such names as roots, rami, trunks, and branches) are actually composed of orderly arrangements of the axonal and dendritic processes of many nerve cell bodies. The cell bodies of peripheral neurons are often found grouped into clusters called ganglia. Based on the type of nerve cell bodies found in ganglia, they may be classified as either sensory or motor. Sensory ganglia are found as oval swellings on the dorsal roots of spinal nerves, and they are also found on the roots of certain cranial nerves. The sensory neurons making up these ganglia are unipolar. Shaped much like a golf ball on a tee, they have round or slightly oval cell bodies with concentrically located nuclei, and they give rise to a single fibre that undergoes a T-shaped bifurcation, one branch going to the periphery and the other entering the brain or spinal cord. There are no synaptic contacts between neurons in a sensory ganglion. Motor ganglia are associated with neurons of the autonomic nervous system. Many of these are found in the sympathetic trunks, two long chains of ganglia lying along each side of the vertebral column from the base of the skull to the coccyx; these are referred to as paravertebral. Other motor ganglia (called prevertebral) are found near internal organs innervated by their projecting fibres, while still others (called terminal ganglia) are found on the surfaces or within the walls of the target organs themselves. Motor ganglia contain multipolar cell bodies, which have irregular shapes and eccentrically located nuclei and which project several dendritic and axonal processes. Preganglionic fibres originating from the brain or spinal cord enter motor (autonomic) ganglia, where they synapse on multipolar cell bodies. These postganglionic cells, in turn, send their processes to visceral structures. Spinal nerves Sensory input from the body surface, from joint, tendon, and muscle receptors, and from internal organs passes centrally through the dorsal roots of the spinal cord. Fibres from motor cells in the spinal cord exit via the ventral roots and course to their peripheral targets (autonomic ganglia or skeletal muscle). The spinal nerve is formed by the joining of dorsal and ventral roots, and it is the basic structural and functional unit on which the peripheral nervous system is built. Functions of the human nervous system Higher cerebral functions The neurons of the cerebral cortex constitute the highest level of control in the hierarchy of the nervous system. Consequently, the terms higher cerebral functions and higher cortical functions are used by neurologists and neuroscientists to refer to all conscious mental activity of the kind normally described as thinking, remembering, and reasoning and to complex volitional behaviour such as speaking and carrying out purposive movement. They also refer to the processing of information in the cerebral cortex, most of which takes place unconsciously. Analytical approaches Neuroscientists investigate the structure and functions of the cerebral cortex, but the processes involved in thinking are also studied by cognitive psychologists, who group the mental activities known to the neuroscientist as higher cortical functions under the headings cognitive function or human information processing. From this perspective, complex information processing is the hallmark of cognitive function. Cognitive science attempts to identify and define the processes involved in thinking without regard to their physiological basis. The resulting models of cognitive function resemble flowcharts for a computer program more than neural networksand, indeed, they frequently make use of computer terminology and analogies. The discipline of neuropsychology, by studying the relationship between behaviour and brain function, bridges the gap between neural and cognitive science. Examples of this bridging role include studies in which cognitive models are used as conceptual frameworks to help explain the behaviour of patients who have suffered damage to different parts of the brain. Thus, damage to the frontal lobes can be conceptualized as a failure of the central executive component of working memory, and a failure of the generate function in another model of mental imagery would fit with some of the consequences of left parietal lobe damage. The analysis of changes in behaviour and ability following damage to the brain is by far the oldest and probably the most informative method adopted for studying higher cortical functions. Usually these changes take the form of what is known as a deficitthat is, an impairment of the ability to act or think in some way. With certain provisos, one can assume that the damaged part of the brain is involved in the function that has been lost. However, people vary considerably in their abilities, and most brain lesions occur in subjects whose behaviour has not been formally studied before they become ill. Lesions are rarely precisely congruent with the brain area responsible for a given function, and their exact location and extent can be difficult to determine even with modern imaging techniques. Abnormal behaviour after brain injury, therefore, is often difficult to attribute to precisely defined damage or dysfunction. It would also be naive to suppose that a function is represented in a particular brain area just because it is disrupted after damage to that area. For example, a tennis champion does not play well with a broken ankle, but this would not lead one to conclude that the ankle is the centre in which athletic skill resides. Reasonably certain conclusions about brainbehaviour relationships, therefore, can be drawn only if similar well-defined changes occur reliably in a substantial number of patients suffering from similar lesions or disease states. The most prominent series of observations clearly belonging to modern neuropsychology were made by Paul Broca in the years following 1861. He reported the cases of several patients whose speech had been affected following damage to the left frontal lobe and provided autopsy evidence of the location of the lesion. In making his famous statement, We speak with the left hemisphere, he explicitly recognized the left hemisphere's control of language, one of the fundamental phenomena of higher cortical function. In 1874, the German neurologist Carl Wernicke described a case in which a lesion in a different part of the left hemisphere, the posterior temporal region, affected language in a different way. In contrast to Broca's cases, language comprehension was more affected than language output. This meant that two different aspects of higher cortical function had been found to be localized in different parts of the brain. In the next few decades there was a rapid expansion in the number of cognitive processes studied and tentatively localized. Wernicke was one of the first to recognize the importance of the interaction between connected brain areas and to think of higher cortical function as the buildup of complex mental processes through the coordinated activities of local regions dealing with relatively simple, predominantly sensory-motor functions. In doing so, he opposed the view of the brain as an equipotential organ acting en masse. Since his time, scientific fashion has swung between the localization and mass-action theories. Major changes in the 20th century have been both quantitative, with vast increases in knowledge, and methodological, with the discovery of new ways of studying the brain's anatomy and physiology and the introduction of better quantitative methods in the study of behaviour. Functions of the human nervous system The autonomic system The autonomic nervous system is regulated by cell groups in the brain that process visceral information arriving in specific neural networks, integrate that information, and then issue specific regulatory instructions through the appropriate autonomic outflows. Each end organ is processed in a unique way by functionally specific sets of neurons in which there is often coordination of both the sympathetic and parasympathetic nervous systems. The eye In order for the eye to function properly, specific autonomic functions must maintain adjustment of four types of smooth muscle: (1) smooth muscle of the iris, which controls the amount of light that passes through the pupil to the retina; (2) ciliary muscle on the inner aspect of the eye, which controls the ability to focus vision on nearby objects; (3) smooth muscle of arteries providing oxygen to the eye; and (4) the smooth muscle of veins that drain blood from the eye and affect intraocular pressure. In addition, the cornea must be kept moist by adequate secretion from the lacrimal gland. Functions of the human nervous system The vestibular system Animals have evolved sophisticated sensory receptors to detect features of the environment in which they live. In addition to the special senses such as hearing and sight, there are unobtrusive sensory systems such as the vestibular system, which is sensitive to acceleration. Acceleration can be considered as occurring in two formslinear and angular. One familiar type of linear acceleration is gravity. Because this environmental feature, unlike any other encountered by an organism, is always present, highly sophisticated systems have developed to detect gravity and enable an animal to maintain its position relative to the earth. A common form of angular acceleration is that induced by rotation, such as a turning of the head. Through the vestibular apparatus these forces are detected and appropriate motor activities are organized to counter the postural perturbations that they induce. Receptors The vestibular sensory organ is a paired structure located symmetrically on either side of the head within the inner ear. Inside each end organ are the hair cells, the detection units for both linear and angular acceleration. Extending from one surface of each hair cell are fine, hairlike cilia, displacement of which alters the electrical potential of the cell. Bending the cilia in one direction causes the cell membrane to depolarize while hyperpolarization is induced by movement in the opposite direction. Changes in membrane potential induce alteration in the firing of nerve impulses by the afferent neurons supplying each hair cell. The two types of acceleration are detected by two types of vestibular end organ. Linear acceleration is sensed by a pair of organsthe saccule and utriclewhile there are three receptor organscalled semicircular canalsin each vestibular apparatus for the detection of angular acceleration. Functions of the human nervous system Pain Theories of pain There have always been two theories of the sensation of pain, a quantitative or intensity theory and a stimulus-specific theory. According to the former, pain results from excessive stimulation of every kind: e.g., excessive heat or cold, excessive damage to the tissues. This theory in its simplest form entails the belief that the same afferent nerve fibres are activated by all of these various stimuli; pain is felt merely when they are conducting far more impulses than usual. But knowledge acquired in the 20th century has shown that the quantitative theoryat least in its classic formis wrong. Peripheral nerve fibres have been found to be stimulus-specific, each one excited by certain forms of energy. The stimulus-specific theory proposes that pain results from interactions between various impulses arriving at the spinal cord and brain, that these impulses are brought to the spinal cord in certain non-myelinated and small myelinated fibres, and that the specific stimuli that excite these nerve fibres are noxious, or harmful. In the somatic tissues there are certain kinds of nerve fibre that do not give rise to pain, no matter how many there are or how frequently they are stimulated. Included in this category are mechanoreceptors that report only deformation of the skin and the larger afferent nerve fibres from muscles and tendons that form part of the organization of posture and movement. No matter how they are excited, these receptors never give rise to pain. But the smaller fibres from these tissues do cause pain when they are excited mechanically or chemically. Warmth and cold fibres are specific. Warmth fibres are excited by rising temperature and quieted by falling temperature, and cold fibres respond similarly with cold stimuli. Although pain arises from very hot and very cold stimulation and with intense forms of mechanical stimulation, this occurs only with the activation of afferent nerve fibres that specifically report noxious events. When no noxious events are occurring, these nerve fibres are silent. In contrast, the quantitative theory seems to apply to the viscera, where afferent nerve fibres used in reflex organization also report events giving rise to pain. In the heart, for example, the same nerve fibres are excited by mechanical stimulation as are excited by chemical substances formed in the body that cause pain. Also, in the bladder, rectum, and colon, nerve fibres activated by substances that cause pain are the same as those activated by distension and contraction of the viscera. This means that the same nerve fibres are reporting the state that underlies the desire to urinate or defecate and the sensation underlying the pain felt when these organs are strongly contracting in an attempt to evacuate their contents. In the heart, rectum, and bladder, therefore, pain appears to be due to a summation of impulses in sensory nerve fibres and is not mediated by a special group of fibres reserved for reporting noxious events. It must be pointed out, however, that not all researchers accept the argument. Lower-level pain pathways Tissues Normal conditions Not all the tissues making up the body give rise to pain; furthermore, each tissue must be stimulated in an appropriate way to invoke its particular sensation of pain. Skin, being the outer covering of the body, easily raises the warning of pain, but other tissues that do not come in direct contact with the outer environment are just the opposite. The brain, for example, can be pierced, cut, and burned in neurosurgery, while the patient would require only local anesthesia of the pain-sensitive scalp. The lung, liver, and spleen also do not give rise to pain, no matter how they are stimulated. Pain arises from hollow viscera when the passage of their contents is obstructed and the musculature must undergo strong contraction and stretching. Pain cannot be induced by cutting or burning the wall of the intestine, but pulling on the mesenteric tissue that fixes the intestines to the posterior wall of the abdomen causes pain. The reason for these differences is clear. Tissues are sensitive to the kinds of damage they are likely to meet during life and not to those that they probably will never meet. Although the warning function of pain is obvious, it is not equivalent to nociception, the perception of forces likely to damage the tissues of the body. First, nociception can occur without pain and pain without nociception; also, the sensation of pain is only a part of the total act of nociception. There are reflex effects as well, such as a local reflex withdrawal from a sudden noxious stimulation of the skin. There are autonomic effects, such as a rise in blood pressure, quickening of the heart rate and respiration, and other excitatory sympathetic nervous effects. There may even be shrieking or howling, warning other animals that something dangerous and painful is occurring. Functions of the human nervous system The human nervous system differs from that of other mammals chiefly in the great enlargement and elaboration of the cerebral hemispheres. Much of what is known of the function of the brain is derived from observations of the effects of disease or by analogy with the results of experimentation on animals, particularly the monkey. Such sources of information are clearly inadequate for the elucidation of the nervous activity underlying many properties of the human brainparticularly speech and mental processes. It is not surprising, therefore, that knowledge of the functions of this uniquely complex system, although rapidly expanding, is far from complete. In the following account of the functions of the human nervous system, there are numerous references to tracts and to less well-defined connections between different regions of the brain and spinal cord. The identification of these pathways is not always a simple matter; indeed, in humans, many are incompletely known or are simply conjectural. A great deal of information has been obtained by observing the spreading effects of axonal destruction. If a nerve fibre is severed, the length of axon farthest from the cell body, or soma, will be deprived of the axonal flow of metabolites and will begin to break up. The myelin sheath will also degenerate, so that, for some months after the injury, breakdown products of myelin will be seen under the microscope with special stains. This method is obviously of limited application in humans, as it requires precise lesions and subsequent examination before the myelin has been completely removed. The staining of degenerated axons and of the terminals that form synapses with other neurons is also possible using silver impregnation, but the techniques are laborious and results sometimes difficult to interpret. That a damaged neuron should show degenerative changes, however difficult to detect, is not unexpected, but the interdependence of neurons is sometimes shown by transneuronal degeneration. Neurons deprived of major input from axons that have been destroyed may themselves atrophy. This phenomenon is called anterograde degeneration. In retrograde degeneration, similar changes may occur in neurons that have lost the main recipient of their outflow. These anatomical methods are occasionally applicable to human disease. They can also be used postmortem when lesions in the central nervous system have been deliberately madefor example, in the surgical treatment of intractable pain. Some more recently developed techniques can be used only in experiments on animals, but these are not always relevant to humans. For example, normal biochemical constituents labeled with a radioactive isotope can be injected into neurons and then transported the length of the axon, where they can be detected by picking up the radioactivity on an X-ray plate. An observation technique dependent on retrograde axonal flow has been used extensively to demonstrate the origin of fibre tracts. In this technique, the enzyme peroxidase is taken up by axon terminals and is transported up the axon to the soma, where it can be shown by appropriate staining. The staining of neurotransmitter substances is possible in postmortem human material as well as in animals and is an important method. Success, however, is dependent on examining relatively fresh or frozen material, and results may be greatly affected by previous treatment with neurologically active drugs. Electrical stimulation of a region of the nervous system gives rise to the generation of nerve impulses in centres receiving input from the site of stimulation. This method, using microelectrodes, has been widely used in animal studies. The precise path followed by the artificially generated impulse may be difficult to establish. Receptors Receptors are biological transducers, converting the various kinds of energy they receive from the external and internal environments into electrical impulses. They are of many kinds and are classified in many ways. Steady-state receptors, for example, generate impulses as long as a particular state such as temperature remains constant. Changing-state receptors, on the other hand, respond to variation in the intensity or position of the stimulus. Receptors are also classified as exteroceptive (reporting the external environment), interoceptive (sampling the environment of the body itself), and proprioceptive (sensing the posture and movements of the body). Exteroceptors are used for looking, listening, smelling, tasting, touching, and feeling. Interoceptors report the state of the bladder, the alimentary canal, the blood pressure, and the osmotic pressure of the blood plasma. Proprioceptors report the position and movements of parts of the body and the position of the body in space. Receptors are also classified according to the kinds of stimulus to which they are sensitive. Chemical receptors, or chemoreceptors, are sensitive to substances taken into the mouth (taste or gustatory receptors), inhaled through the nose (smell or olfactory receptors), or found in the body itself (detectors of glucose or of acidbase balance in the blood). Receptors of the skin are classified as thermoreceptors, mechanoreceptors, and nociceptorsthe last being sensitive to stimulation that is noxious, or likely to damage the tissues of the body. Thermoreceptors of the skin are of two kinds, warmth and cold. Warmth fibres are excited by rising temperature and inhibited by falling temperature, and cold fibres respond in the opposite manner. Mechanoreceptors in the skin are also of several different types. Sensory nerve terminals around the base of hairs are activated by very slight movement of the hair, but they rapidly adapt to continued stimulation and stop firing. In hairless skin there are both rapidly and slowly adapting receptors. These can provide information about the force of mechanical stimulation. The Pacinian corpuscles, elaborate structures found in the skin of the fingers but also in other organs, are layers of fluid-filled membranes forming structures just visible to the naked eye at the terminals of axons. The precise function of the corpuscles is not fully known, but they are probably activated by rapidly changing or alternating stimuli such as vibration. In some places receptors are massed together to form a sense organ, such as the eye or ear. At other places they are scattered, as are those of the skin and viscera. Receptors are connected to the central nervous system by afferent nerve fibres. The region or area in the periphery from which a neuron within the central nervous system receives input is called its receptive field. Receptive fields are changing and not fixed entities. All receptors report two features of stimulation, its intensity and its site. Intensity is signaled by the frequency of nerve impulse discharge in a neuron and also by the number of afferent nerves reporting the stimulation. As the strength of a stimulus increases, the change in electrical potential of the receptor increases, and the frequency of nerve impulse generation likewise increases. The location of a stimulus, whether in the environment or in the body, is readily resolved by the nervous system. Localization of stimuli in the environment depends to a great extent on having pairs of receptors, one on each side of the body. For example, people in early childhood learn that a loud sound is probably coming from a nearer source than a weak sound. They localize the sound by noticing the difference in intensity and the minimal difference in time of arrival at the ears, increasing these differences by turning the head. Localization of a stimulus on the skin depends upon the arrangement of nerve fibres in the skin and in the deep tissues beneath the skin, as well as upon the overlap of receptive fields. Most mechanical stimuli indent the skin, stimulating nerve fibres in the connective tissue below the skin. Any point on the skin is supplied by at least three, and sometimes up to 40, nerve fibres, and no two points are supplied by precisely the same pattern of fibres. Finer localization is achieved by what is called surround inhibition. In the retina, for example, there is an inhibitory area around the excited area. This mechanism accentuates the excited area, making it stand out. There can also be a mechanism called surround excitation, in which a central area is inhibited and the surrounding area excited. In both cases contrast is brought out and discrimination sharpened. In seeking information about the environment, the nervous system presents the most sensitive receptors to a stimulating object. At its simplest, this action is reflex. In the retina is a small region about the size of a pinhead, called the fovea, which is particularly sensitive to colour. When a part of the periphery of the visual field is excited, a reflex movement of the head and eyes focuses the light rays upon that part on the fovea. A similar reflex turns the head and eyes in the direction of a noise. As the English physiologist Charles Sherrington said in 1900, In the limbs and mobile parts, when a spot of less discriminative sensitivity is touched, instinct moves the member, so that it brings to the object the part where its own sensitivity is delicate. . . .