15: The Organization of the Central Nervous System

• The Central Nervous System Consists of the Spinal Cord and the Brain

• The Major Functional Systems Are Similarly Organized

  • Information Is Transformed at Each Synaptic Relay

  • Neurons at Each Synaptic Relay Are Organized into a Neural Map of the Body

  • Each Functional System Is Hierarchically Organized

  • Functional Systems on One Side of the Brain Control the Other Side of the Body

• The Cerebral Cortex Is Concerned with Cognition

  • Neurons in the Cerebral Cortex Are Organized in Layers and Columns

  • The Cerebral Cortex Has a Large Variety of Neurons

• Subcortical Regions of the Brain Are Functionally Organized into Nuclei

• Modulatory Systems in the Brain Influence Motivation, Emotion, and Memory

• The Peripheral Nervous System Is Anatomically Distinct from the Central Nervous System

• An Overall View

In the earlier chapters of this book we emphasized that modern neuroscience is based importantly on two tenets. First, the brain is organized into functionally specific areas, and second, neurons in different parts of the vertebrate nervous system, indeed in all nervous systems, are quite similar. What distinguishes one functionally distinct brain region from another, and one brain from the next, are the number and types of neurons in each and how they are interconnected through development. The specific patterns of interconnection and the resulting functional organization of neural circuits in distinct brain regions underlie the individuation of behavior.

All behavior, from simple reflex responses to complex mental acts, is the product of signaling between appropriately interconnected neurons. Consider the simple act of hitting a tennis ball (Figure 15–1). Visual information about the motion of the approaching ball is analyzed in the visual system. This information is combined with proprioceptive information about the position of the arms, legs, and trunk to calculate the movement necessary to intercept the ball. Once the swing is initiated, many minor adjustments of the motor program are made based on a steady stream of sensory information about the trajectory of the approaching ball. Finally, this entire act is accessible to consciousness, and thus may elicit memories and emotions. Of course, as the swing is being executed, the brain is also engaged in maintaining the player's heart rate, respiration, and other autonomic functions that are typically outside the awareness of the player.

Thus, to understand the neural control of any behavior it is necessary to break down that behavior into key components, to then identify the regions of the brain responsible for each component, and to analyze the neural connections between those regions. Although the anatomy of the brain and its interconnections appear complex, brain anatomy is easier to grasp if one understands the relatively simple set of principles that underlie the fundamental organization of the nervous system. In this and the next five chapters we examine the relationship between anatomy and behavior in a series of progressively more complex examples.

In this chapter and the next we review the major anatomical components of the central nervous system by outlining the organization of the major functional systems that recruit these components. In Chapters 17 and 18 we examine how complex cognitive functions are constructed from the interaction of cortical association areas. In Chapter 19 we describe how in higher cortical association areas perception—the product of the sensory systems—and action—the product of the motor systems—work in parallel. Finally, in Chapter 20 we explore how complex cognitive functions of humans, including attention and consciousness, can be studied by means of brain imaging.

The location and orientation of components of the central nervous system within the body are described with reference to three axes: the rostral-caudal, dorsal-ventral, and medial-lateral axes (Figure 15–2).

The spinal cord is the most caudal part of the central nervous system and in many respects the simplest part. It extends from the base of the skull to the first lumbar vertebra. The spinal cord receives sensory information from the skin, joints, and muscles of the trunk and limbs, and contains the motor neurons responsible for both voluntary and reflex movements. Along its length the spinal cord varies in size and shape, depending on whether the emerging motor nerves innervate the limbs or trunk; it is thicker at levels that innervate the arms and legs.

The spinal cord is divided into a core of central gray matter and surrounding white matter. The gray matter, which contains nerve cell bodies, is typically divided into dorsal and ventral horns (so-called because the gray matter appears H-shaped in transverse sections). The dorsal horn contains an orderly arrangement of sensory relay neurons that receive input from the periphery, whereas the ventral horn contains groups of motor neurons and interneurons that regulate motor neuronal firing patterns. The axons of motor neurons innervate specific muscles. The white matter is made up in part of rostral-caudal (longitudinal) ascending and descending tracts of myelinated axons. The ascending pathways carry sensory information to the brain, while the descending pathways carry motor commands and modulatory signals from the brain to the muscles.

The nerve fibers to and from the spinal cord are bundled in 31 spinal nerves, each of which has a sensory and a motor division. The sensory division (the dorsal root) carries information from muscles and skin into the spinal cord and terminates in the dorsal aspect of the cord. Different classes of axons within the dorsal roots convey pain, temperature, touch, and visceral sensory information. The motor division (the ventral root) emerges from the ventral aspect of the cord and comprises the axons of motor neurons that innervate muscles. Ventral roots from certain levels of the spinal cord also include sympathetic and parasympathetic axons. The motor neurons of the spinal cord comprise the "final common pathway" through which all higher brain levels controlling motor activity must act.

The brain, which lies rostral to the spinal cord, is composed of six regions: the medulla, pons, midbrain, cerebellum, diencephalon, and cerebral hemispheres or telencephalon (Figure 15–3). Each of these divisions is found in both hemispheres of the brain with slight bilateral differences. Each of the six divisions is further subdivided into several anatomically and functionally distinct areas.

The three divisions of the central nervous system immediately rostral to the spinal cord—the medulla, pons, and midbrain—are collectively termed the brain stem.

The medulla, the most caudal portion of the brain stem, is a direct extension of the spinal cord and resembles the spinal cord both in organization and function. Neuronal groups in the medulla participate in regulating blood pressure and respiration. The medulla also contains neuronal groups that are early components of pathways that mediate taste, hearing, and maintenance of balance as well as the control of neck and facial muscles.

The pons lies rostral to the medulla and protrudes from the ventral surface of the brain stem. The ventral portion of the pons contains the pontine nuclei, groups of neurons that relay information about movement and sensation from the cerebral cortex to the cerebellum. The dorsal portion of the pons contains structures involved in respiration, taste, and sleep.

The midbrain, the smallest part of the brain stem, lies rostral to the pons. Nuclei in the midbrain provide important linkages between components of the motor system, particularly the cerebellum, basal ganglia, and cerebral hemispheres. For example, the substantia nigra provides important input to a portion of the basal ganglia that regulates voluntary movements. The substantia nigra is the focus of intense interest as damage to its dopaminergic neurons is responsible for the pronounced motor disturbances that are characteristic of Parkinson disease (see Chapter 43). The midbrain also contains components of the auditory and visual systems. Finally, several regions of the midbrain give rise to pathways that are connected to the extraocular muscles that control eye movements.

The brain stem has five distinct functions. First, just as the spinal cord mediates sensation and motor control of the trunk and limbs, the brain stem mediates sensation and motor control of the head, neck, and face. The sensory input and motor output of the brain stem is carried by 12 cranial nerves that are functionally analogous to the 31 spinal nerves. Second, the brain stem is the site of entry for information from several specialized senses, such as hearing, balance, and taste. Third, specialized neurons in the brain stem mediate parasympathetic reflexes, such as decreases in cardiac output and blood pressure, increased peristalsis of the gut, and constriction of the pupils. Fourth, the brain stem contains ascending and descending pathways that carry sensory and motor information to other divisions of the central nervous system. Fifth, a relatively diffuse network of neurons distributed throughout the core of the brain stem, known as the reticular formation, receives a summary of much of the incoming sensory information and is important in regulating alertness and arousal.

The cerebellum lies over the pons and is divided into several lobes by distinct fissures. The cerebellum is important for maintaining posture and coordinating head, eye, and arm movements, and is also involved in minute regulation of motor output and learning motor skills. Until recently, the cerebellum was considered a purely motor structure, but new anatomical information about its interconnections with the cerebral cortex and functional imaging studies have shown that it is also involved in language and other cognitive functions. The cerebellum contains far more neurons than any other single subdivision of the brain, including the cerebral hemispheres. Its internal circuitry, however, is well understood because relatively few types of neurons are involved. The cerebellum receives information about somatic sensation from the spinal cord, information about balance from the vestibular organs of the inner ear, and motor and sensory information from various areas of the cerebral cortex via the pontine nuclei.

The diencephalon contains two major subdivisions: the thalamus and hypothalamus. The thalamus is an essential link in the pathway of sensory information from the periphery (other than olfactory receptors in the nose) to sensory regions of the cerebral hemispheres. It once was thought to act only as a relay station for sensory information traveling to the neocortex, but now it is clear that it also determines which sensory information reaches the neocortex. The thalamus also interconnects the cerebellum and basal ganglia with regions of the cerebral cortex concerned with movement and cognition. Like the reticular formation, the diencephalon also has regions that are thought to influence levels of attention and consciousness.

The hypothalamus lies ventral to the thalamus and regulates homeostasis and several reproductive behaviors. For example, it plays an important role in somatic growth, eating, drinking, and maternal behavior by regulating the hormonal secretions of the pituitary gland. The hypothalamus also influences behavior through its extensive afferent and efferent connections with practically every region of the central nervous system. It is an essential component of the motivational systems of the brain, initiating and maintaining behaviors the organism finds aversive or rewarding. Finally, one group of neurons in the hypothalamus, the suprachiasmatic nucleus, regulates circadian rhythms, cyclical behaviors that are entrained to the daily light–dark cycle.

The cerebral hemispheres are the largest part of the human brain. They consist of the cerebral cortex, the underlying white matter, and three deep-lying structures: the basal ganglia, amygdala, and hippocampal formation. The cerebral hemispheres have perceptual, motor, and cognitive functions, including memory and emotion. The two hemispheres are interconnected by the corpus callosum, which is visible on the medial surface of the hemispheres. The corpus callosum is the largest of the commissures (large bundles of axons that mainly link similar regions of the left and right sides of the brain). The amygdala is concerned with the expression of emotion, the hippocampus with memory formation, and the basal ganglia with the control of movement and aspects of motor learning.

While the spinal cord, brain stem, and diencephalon mediate many life-sustaining functions, it is the cerebral cortex—the thin outer layer of the cerebral hemispheres—that is responsible for much of the planning and execution of actions in everyday life. The cerebral cortex is divided into four major lobes—frontal, parietal, temporal, and occipital—named after the overlying cranial bones (Figure 15–4). Each lobe includes many distinct functional subregions. The temporal lobe, for example, has distinct regions with auditory, visual, or memory functions.

Two additional regions of the cerebral cortex are the cingulate cortex, which surrounds the dorsal surface of the corpus callosum and is involved in the regulation of emotion and cognition, and the insular cortex (insula), which is not visible on the surface owing to the overgrowth of the frontal, parietal, and temporal lobes (Figure 15–5) and is concerned with emotion and the regulation of homeostasis. The overhanging portion of the cerebral cortex that buries the insula within the lateral sulcus is called the operculum.

Although the cerebral cortex on both sides of the brain is generally similar, some areas of cortex on the two sides are functionally distinct. In right-handed people, for example, portions of the left cerebral cortex are specialized for language, whereas the right side of the brain is more related to visuospatial information processing.

In the mid-19th century Pierre Paul Broca first called attention to portions of the frontal, parietal, and temporal lobes that encircle the fluid-filled ventricles of the brain, forming a continuous region at the border of the cerebral cortex. He named this region the limbic lobe (Latin limbus, border). The limbic lobe is no longer considered one of the major subdivisions of the cerebral cortex. However, the cingulate gyrus, which surrounds the corpus callosum and occupies much of Broca's limbic lobe (Figure 15–4), is a separate division of the neocortex, much like the insular cortex.

Distinct functional components of the neural system are connected to each other via discrete pathways, that is, tracts of bundled axons from one discrete population of neurons that terminate in another discrete population. Some of these pathways are very large and can be seen with the unaided eye in the gross brain. The pyramidal tracts, for example, project conspicuously from the cerebral cortex to the spinal cord. Most pathways are not nearly as prominent but can be demonstrated with neuroanatomical tracing techniques (see Box 4–2).

The central nervous system consists of several functional systems that are relatively autonomous. There are, for example, discrete systems for each of the five special senses (touch, vision, hearing, taste, smell), for different classes of movement (eye movements, arm movements, hand movements), and for language. Each functional system comprises numerous interconnected anatomical sites throughout the brain.

These several functional systems of the brain must act together cooperatively. In sensory systems, for example, sensory neurons in the periphery project, directly or indirectly, to one or more regions in the spinal cord, brain stem, and thalamus. The thalamus projects to the primary sensory areas of cerebral cortex, which in turn project to other regions of cortex.

Information Is Transformed at Each Synaptic Relay

The output of each synaptic relay in a functional pathway is rarely the same as its input. For example, information may be amplified or attenuated depending on the arousal level of the animal. A single neuron typically receives signals from thousands of presynaptic neurons, and the summation of all of these inputs determines the output of the neuron. The information encoded by each successive neuron in a functional pathway is typically more complex than the output of the preceding neuron.

Neurons at Each Synaptic Relay Are Organized into a Neural Map of the Body

One of the most striking features of the organization of most sensory systems is that the inputs from peripheral receptive surfaces—the retina of the eye, the cochlea of the inner ear, and the surface of the skin—are arranged topographically throughout successive stages of processing. Neighboring groups of cells in the retina, for example, project to neighboring groups of cells in nuclei of the thalamus, which, in turn, project to neighboring regions of the visual cortex. In this way the neurons at each successive relay of a sensory pathway form an orderly neural map of information from the receptive surface.

These neural maps reflect not only the spatial arrangement of receptors but also the variation in receptor density throughout the receptive surface. The density of innervation in an area of skin, for example, determines the degree of sensitivity of that area to tactile stimuli. The central region of the retina, the fovea, has the highest density of photoreceptors of any part of the retina and thus the greatest visual acuity. Correspondingly, the area of visual cortex devoted to information from the fovea is greater than the areas representing the peripheral portions of the retina, where the density of receptors (and visual acuity) is lower.

Similarly, in successive stages of cortical motor pathways the neurons that regulate particular body parts are clustered together to form a motor map; the most well-defined motor map is in the primary motor cortex. Motor maps, like sensory maps, do not represent every part of the body equally. The extent of the representation of a body part in a motor map reflects the density of innervation of that part, and thus the fineness of control required for movements in that part.

Each Functional System Is Hierarchically Organized

Information processing in sensory and motor systems is organized hierarchically. Within a system some areas of the cerebral cortex are designated as primary, secondary, or tertiary areas, depending on their functional sequence within the pathway. For example, the primary motor cortex mediates voluntary movements of the limbs and trunk; it is called primary because it contains neurons that directly activate somatic motor neurons in the spinal cord. The primary sensory areas receive most of their information from the thalamus, which receives signals from the peripheral receptors with only a few intervening synaptic relays. Whereas the primary sensory areas of cortex are the initial site of cortical processing of sensory information, the primary motor cortex is the final site in the cortex for processing motor commands.

The primary visual cortex is located caudally in the occipital lobe and is predominantly associated with the prominent calcarine sulcus (see Figure 15–4). The primary auditory cortex is located in the temporal lobe, where it is associated with a series of gyri (Heschl's gyri) on the lateral sulcus. The primary somatosensory cortex is located caudal to the central sulcus on the postcentral gyrus, in the parietal lobe.

Each primary sensory area conveys information to an adjacent, higher-order area, a unimodal association area where individual neurons selectively encode specific features of sensory stimuli and together represent complex information. At very advanced stages of the visual system, individual neurons are responsive to highly integrated information, such as the shape of a face.

Each higher-order sensory area sends its outputs to one or another of three major multimodal association areas that integrate information from two or more sensory modalities and coordinate this information with plans for action (see Chapter 18). Complex sensory information is also sent to higher-order motor areas, located rostral to the primary motor cortex in the frontal lobe, where programs for movement, or potential movements, are calculated and conveyed to the primary motor cortex for implementation. Some of the motor areas in the frontal lobe also send commands directly to the spinal cord. Cells in the primary motor cortex influence neurons in the ventral horn of the spinal cord responsible for muscle movements, and thus the primary motor cortex is intimately associated with the motor systems of the spinal cord.

Functional Systems on One Side of the Brain Control the Other Side of the Body

Most pathways in the central nervous system are bilaterally symmetrical and cross over to the opposite (contralateral) side of the brain or spinal cord. As a result, sensory and motor activities on one side of the body are mediated by the cerebral hemisphere on the opposite side. Thus, movement on the left side of the body is largely controlled by neurons in the right motor cortex.

The pathways of different systems cross at different anatomical levels within the brain. For example, the ascending pathways for pain cross in the spinal cord almost immediately upon entering the central nervous system. The sensory pathway for fine touch, however, ascends on the same side of the spinal cord that it enters. At the medulla, where it makes its first synapse, second-order fibers cross over to the thalamus on the contralateral side. Crossings of this kind within the brain stem and spinal cord are called decussations.

Phylogenetically, humans have the most elaborate cerebral cortex. The four lobes of the cerebral cortex have a highly convoluted shape, formed by indentations or grooves (sulci) that separate elevated regions (gyri) , which occupy a relatively consistent position across individuals. One of the most prominent indentations, the lateral sulcus or sylvian fissure, separates the temporal lobe from the frontal and parietal lobes (see Figure 15–4). Another prominent indentation, the central sulcus, runs medially and laterally on the dorsal surface of the hemisphere and separates the frontal and parietal lobes.

It is likely that this convoluted shape arose during evolution as a strategy for packing ever-increasing numbers of neurons into the limited space of the skull, as the thickness of the cortex does not vary substantially in different species (always approximately 2 to 4 mm thick), although the surface area is dramatically larger in higher primates, particularly in humans. By allowing for a greater number of cortical neurons, an increase in the surface area of the cortex provides a greater capacity for processing information.

Neurons in the Cerebral Cortex Are Organized in Layers and Columns

The neocortex—the region of cerebral cortex nearest the surface of the brain—is organized into layers and columns, an arrangement that increases the computational efficiency of the cerebral cortex. As we shall see below, the subcortical regions have a nuclear organization.

The neocortex receives inputs from the thalamus, other cortical regions on both sides of the brain, and other structures. Its output is directed to other regions of the neocortex, basal ganglia, thalamus, pontine nuclei, and the spinal cord. These complex input–output relationships are efficiently organized in the orderly layer ing of cortical neurons; each layer contains different inputs and outputs. Most of the neocortex contains six layers, numbered from the outer surface (pia mater) of the cortex to the white matter (Figure 15–6).

Layer I, the molecular layer, is occupied by the dendrites of cells located in deeper layers and axons that travel through this layer to make connections in other areas of the cortex.

Layers II and III contain mainly small pyramidal shaped cells. Layer II, the external granular cell layer, is one of two layers that contain small spherical neurons. Layer III is called the external pyramidal cell layer (an internal pyramidal cell layer lies at a deeper level). The neurons located deeper in layer III are typically larger than those located more superficially. The axons of pyramidal neurons in layers II and III project locally to other neurons within the same cortical area as well as to other cortical areas, thereby mediating intracortical communication (Figure 15–7).

Layer IV contains a large number of small spherical neurons and thus is called the internal granular cell layer. It is the main recipient of sensory input from the thalamus and is most prominent in primary sensory areas. For example, the region of the occipital cortex that functions as the primary visual cortex has an extremely prominent layer IV (Figure 15–8). Layer IV in this region is so heavily populated by neurons and so complex that it is typically divided into three sub-layers. Areas with a prominent layer IV are called granular cortex. In contrast the precentral gyrus, the site of the primary motor cortex, has essentially no layer IV (Figure 15–8) and is thus part of the so-called agranular frontal cortex. These two cortical areas are among the easiest to identify in histological sections.

Layer V, the internal pyramidal cell layer, contains mainly pyramidally shaped cells that are typically larger than those in layer III. Pyramidal neurons in this layer give rise to the major output pathways of the cortex, projecting to other cortical areas and to subcortical structures (Figure 15–7).

The neurons in layer VI are fairly heterogeneous and thus this layer is called the polymorphic or multiform layer. It blends into the white matter that forms the deep limit of the cortex and carries axons to and from areas of cortex.

Although each layer of the neocortex is defined primarily by the presence, absence, and packing density of distinctive cell types, each layer also contains the dendrites of specific cortical neurons. Layers I through III contain the apical dendrites of neurons that have their cell bodies in layers V and VI, as well as in layers II and III, whereas layers V and VI contain the basal dendrites of neurons with cell bodies in layers III and IV, as well as in layers V and VI (Figure 15–7). The inputs to a cortical neuron thus depend on the location of its dendrites and cell body.

The thickness of individual layers and the details of their functional organization vary throughout the cortex. An early student of the cerebral cortex, Korbinian Brodmann, used the relative prominence of the layers above and below layer IV, cell size, and packing characteristics to distinguish different areas of the neocortex. Based on such cytoarchitectonic differences, Brodmann in 1909 divided the cerebral cortex into 47 regions (Figure 15–8).

Although Brodmann's demarcation coincides, in part, with recent information on localized functions in the neocortex, the cytoarchitectonic method alone does not capture the subtlety or variety of function of all the distinct regions of the cortex. For example, Brodmann identified five regions (areas 17–21) as being concerned with visual function in the monkey. In contrast, modern connectional neuroanatomy and electrophysiology have identified more than 35 functionally distinct cortical regions within the five regions studied by Brodmann.

Within the neocortex information passes from one synaptic relay to another using feedforward and feedback connections. In the visual system, for example, feedforward projections from the primary visual cortex to secondary and tertiary visual areas originate mainly in layer III and terminate mainly in layer IV of the target cortical area. In contrast, feedback projections to earlier stages of processing originate from cells in layers V and VI and terminate in layers I, II, and VI (Figure 15–9).

Neurons in the neocortex are often organized into columns that run from the white matter to the pial surface, thus traversing the layers. (This columnar organization is not particularly evident in standard histological preparations.) Each column is a fraction of a millimeter in diameter. Neurons within a column tend to have very similar response properties, presumably because they form a local processing network. Columns are thought to be the fundamental computational modules of the neocortex (see Chapter 22).

The Cerebral Cortex Has a Large Variety of Neurons

The neurons of the cortex have a variety of shapes and sizes. Raphael Lorente de Nó, a student of Santiago Ramón y Cajal, used the Golgi stain to identify more than 40 different types of cortical neurons based only on the distribution of their dendrites and axons. The neurons of the cortex, as elsewhere, can be broadly defined as either principal (projection) neurons or local interneurons. Projection neurons typically have pyramid-shaped cell bodies (Figure 15–10). They are located mainly in layers III, V, and VI and use the amino acid glutamate as their primary transmitter at excitatory synapses. The axons of principal neurons convey information to the next synaptic relay in the system.

Local interneurons have axons that remain within the same area where their cell body is located and use the neurotransmitter γ-aminobutyric acid (GABA) at inhibitory synapses. These interneurons constitute 20% to 25% of the neurons in the neocortex and are located in all layers. Interneurons may receive inputs from the same sources as the principal cells.

Several types of GABAergic interneurons have been distinguished based on their pattern of connections and the cotransmitters they use with GABA (Figure 15–11). Basket cells form axosomatic synapses, that is, their axons terminate on the cell bodies of target neurons. Other interneurons form axo-axonic synapses, that is, their axons terminate exclusively on the axons of target neurons. The multiple arrays of synaptic terminals formed by these cells resemble a chandelier and thus these cells are typically called chandelier cells.

The neocortex also has a population of excitatory interneurons, located primarily in layer IV. These cells have star-shaped dendritic trees and use glutamate as a transmitter. These excitatory interneurons are the primary recipients of sensory information from the thalamus.

Three major structures lie deep within the cerebral hemispheres: the basal ganglia, the hippocampal formation, and the amygdala. These three subcortical structures act to regulate cortical activity.

Neurons in the basal ganglia regulate movement and contribute to certain cognitive functions such as the learning of motor skills. The basal ganglia receive input from all parts of the cerebral cortex but send their output largely through the thalamus to the frontal lobe. The basal ganglia have five major functional subcomponents: the caudate nucleus, putamen, globus pallidus, subthalamic nucleus, and substantia nigra (Figure 15–12).

The hippocampal formation includes the hippocampus, dentate gyrus, and subiculum. The hippocampus and associated cortical regions form the floor of the temporal horn of the lateral ventricle (Figure 15–12). Together these structures are responsible for the formation of long-term memories about our daily experiences, so-called episodic memories, but are not the permanent storage site of these memories (see Chapter 65). Damage to the hippocampus interferes with people's ability to form new memories but does not significantly impair the ability to retrieve old memories.

The amygdala, which lies just rostral to the hippocampus, is involved in analyzing the emotional or motivational significance of sensory stimuli. It receives input directly from the major sensory systems. Neurons in the amygdala project to the neocortex, basal ganglia, hippocampus, and a variety of subcortical structures including the hypothalamus. Projections to the brain stem can modulate somatic and visceral components of emotion. For example, the amygdala mediates the unconscious responses to danger—changes in heart rate, respiration, and pupillary dilation—as well as the conscious emotional perception of fear.

Thin histological sections through the diencephalon and brain stem reveal the structure of several nuclei. Most nuclei are not homogeneous populations of cells but instead comprise a variety of cells of different sizes and shapes organized into subnuclei, divisions, or layers. A nucleus that appears homo geneous when viewed with the nonspecific Nissl stain (Figure 15–13) may actually prove to be organizationally complex when viewed with other stains that highlight the structure of dendrites (such as the Golgi technique) or the chemical composition of the neurons (such as histochemistry or immunohistochemistry). Neurons in the lateral geniculate nucleus of the thalamus, for example, are grouped into alternating bands of neurons with different functions (Figure 15–14).

The characterization of a nucleus in the brain thus depends on the method by which the neurons are visualized. Indeed, modern neuroanatomy, based on the molecular characterization of different nerve cell types, has contributed greatly to the definition of brain regions. One particularly telling example occurred in the 1970s when Bengt Falck and Nils Hillarp developed a histofluorescence technique for staining monoamine neurotransmitters (see Box 13–2). This technique allowed researchers to deconstruct the reticular formation, a region of the brain stem so named because of its diffuse and seemingly chaotic appearance. We now understand that this region is finely organized into groups of cells characterized by transmitter phenotype (serotonergic, noradrenergic, or dopaminergic). Many other powerful techniques for defining the chemical or genetic composition of neuronal types have emerged in the last few decades. For example, in situ hybridization allows neurons to be visualized based on the genes they express (see Box 13–2). This has led to the tongue-in-cheek saying that "the gains in brain lie mainly in the stain."

Some areas of the brain are neither purely sensory nor purely motor but instead modify specific sensory or motor functions. Modulatory systems are often involved in behaviors that respond to a primary need such as hunger, thirst, or sleep. For example, sensory and modulatory systems in the hypothalamus determine blood glucose levels. When blood sugar drops below a certain critical level, we feel hunger. To satisfy hunger, modulatory systems in the brain focus vision, hearing, and smell on stimuli that are relevant to feeding.

Distinct modulatory systems within the brain stem modulate attention and arousal. Small groups of adrenergic and serotonergic modulatory neurons in the brain stem set the general arousal level of an animal through their connections with forebrain structures. As we will discuss further in Chapter 46, a group of cholinergic modulatory neurons, the basal nucleus of Meynert, is also involved in arousal or attention. It is located beneath the basal ganglia in the basal forebrain portion of the telencephalon. The axons of the neurons in this nucleus project to essentially all portions of the neocortex.

If a predator finds potential prey, a variety of cortical and subcortical systems determine whether the prey is edible. Once food is recognized, other cortical and subcortical systems initiate a comprehensive voluntary motor program to bring the animal into contact with the prey, capture it and place it in the mouth, and chew and swallow.

Finally, the physiological satisfaction the animal experiences in eating reinforces the behaviors that led to the successful predation. A group of dopaminergic neurons in the midbrain are important for monitoring reinforcements and rewards. The power of the dopaminergic modulatory systems has been demonstrated by experiments in which electrodes were implanted into the reward regions of rats and the animals were freely allowed to press a lever to electrically stimulate their brains. They preferred this self-stimulation to obtaining food or water, engaging in sexual behavior, or any other naturally rewarding activity.

How the brain's modulatory systems concerned with reward, attention, and motivation interact with the sensory and motor systems is one of the most interesting questions in neuroscience, one that is also fundamental to our understanding of learning and memory storage. We take up this discussion in detail in Chapter 46

The peripheral nervous system supplies the central nervous system with a continuous stream of information about both the external environment and the internal environment of the body. It has somatic and autonomic divisions (Figure 15–15).

The somatic division includes the sensory neurons that receive information from the skin, muscles, and joints. The cell bodies of these sensory neurons lie in the dorsal root ganglia and cranial ganglia. Receptors associated with these cells provide information about muscle and limb position and about touch and pressure at the body surface. In Part V (Perception) we shall see how remarkably specialized these receptors are in transducing one or another type of physical energy (such as deep pressure or heat) into the electrical signals used by the nervous system. In Part VI (Movement) we shall see that sensory receptors in the muscles and joints are crucial to shaping coherent movement of the body.

The autonomic division of the peripheral nervous system mediates visceral sensation as well as motor control of the viscera, vascular system, and exocrine glands. It consists of the sympathetic, parasympathetic, and enteric systems. The sympathetic system participates in the body's response to stress, whereas the parasympathetic system acts to conserve body resources and restore homeostasis. The enteric nervous system, with neuronal cell bodies located in or adjacent to the viscera, controls the function of smooth muscle of the gut. The functional organization of the autonomic nervous system is described in Chapter 47 and its role in emotion and motivation in Chapters 48 and 49.

The nervous system receives sensory information from the environment, evaluates the significance of the information, and generates appropriate behavioral responses. Accomplishing these tasks requires an anatomical plan of considerable complexity. The human nervous system is comprised of approximately 100 billion neurons, each of which receives and gives rise to thousands of connections. Some of these connections are formed nearly a meter from the cell body of the neuron.

Despite this complexity, the structure of the nervous system is similar in individuals of a species. Knowledge of neuronal structure and the pathways of information flow in the brain is important not only for understanding the normal function of the brain but also for identifying specific regions that are disturbed during neurological illness.

The nervous system has two anatomically distinct components. The central nervous system consists of the brain and spinal cord, while the peripheral nervous system is composed of specialized clusters of neurons (ganglia) and peripheral nerves. The peripheral nervous system relays information to the central nervous system and executes motor commands generated in the brain and spinal cord. Even the simplest behavior involves the integrated activity of several sensory, motor, and functional pathways are precisely arranged synaptic relays made up of clusters or layers of neurons called nuclei. Each functional pathway normally has the same anatomical arrangement in every individual.

Although neuroanatomy may seem to provide only a static picture of the nervous system, it can provide profound insight into how the nervous system functions, in the same way that the detailed structure of proteins reveals important principles of protein function. Understanding brain function therefore depends on an understanding of both structure and function, and crucially, of the relation between the two.

As we shall see in later chapters, modern neuroimaging has revolutionized the study of the cognitive operations of the brain. In particular, positron emission tomography (PET) and magnetic resonance imaging (MRI) have made the functional organization of the intact human brain visible during behavioral experiments. These techniques, in addition to being important tools for diagnosing diseases of the central nervous system, have given us a much clearer idea of the functional specialization of the nervous system. Importantly, they have placed neurology and psychiatry on a firmer empirical footing.