Thus far we have described the structure of individual neurons and their ability to conduct electrical signals. Clearly, neurons never function individually but form interacting circuits referred to as neural networks.
Such complexity allows us to make coordinated responses to changes in the environment. For example, as we perceive a potential danger, we suddenly become vigilant and more acutely aware of our surroundings. Meanwhile, internal organs prepare us for action by elevating heart rate, blood pressure, available energy sources, and so forth. Most of us will also calculate the probable outcome of either fighting or running before taking a defensive or aggressive stance. Even simple responses require a complex coordination of multiple nuclei in ters.
The nervous system comprises the central and peripheral divisions
The nervous system includes the central nervous system or CNS (the brain and spinal cord) and the peripheral nervous system or PNS(all nerves outside the CNS). The PNS in turn can be further divided into the somatic system, which controls voluntary muscles with both spinal nerves and cranial nerves, and the autonomic nervous system, consisting of autonomic nerves and some cranial nerves that control the function of organs and glands. The autonomic nervous system has both sympathetic and parasym-pathetic divisions, which help the organism to respond to changing energy demands. We begin by looking more closely at the peripheral nervous system.
Somatic nervous system Each spinal nerve consists of many neurons, some of which carry sensory information and others motor information; hence they are called mixed nerves. Within each mixed nerve, sensory information is carried from the surface of the body and from muscles into the dorsal horn of the spinal cord by neurons that have their cell bodies in the dorsal root ganglia. These signals going into the spinal cord are called sensory afferents. Mixed nerves also have motor neurons, which are cells beginning in the ventral horn of the spinal cord and ending on skeletal muscles. These are called motor efferents and are responsible for making voluntary movements.
The 12 pairs of cranial nerves that project from the brain provide similar functions as the spinal nerves except that they serve primarily the head and neck; hence they carry sensory information such as vision, touch, and taste into the brain and control muscle movement needed for things like chewing and laughing. They differ from the spinal nerves in that they are not all mixed nerves; several are dedicated to only sensory or only motor function. In addition, several of the cranial nerves innervate glands and organs rather than skeletal muscles, which means they are part of the autonomic nervous system. The most unique cranial nerve is the vagus (nerve X), because it communicates with numerous organs in the viscera, including the heart, lungs, and gastrointestinal tract. The vagus consists of both sensory and motor neurons.
Autonomic nervous system The autonomic nerves, collectively called the autonomic nervous system (ANS), regulate the interna] environment by innervating smooth muscles such as the intestine and urinary bladder, cardiac muscle, and glands, including the adrenal and salivary glands. The purpose of the ANS is to control digestive processes, blood pressure, body temperature, and other functions that provide or conserve energy appropriate to the environmental needs of the organism. The ANS is divided into two components, the sympathetic and parasympathetic divisions, and both divisions serve most organs of the body. Although their functions usually work in opposition to one another, control of our internal environment is not an all-or-none affair. Instead, activity of the sympathetic division predominates when energy expenditure is necessary, such as during times of stress or excitement; hence its nickname is the “fight- or-flight” system. This system increases heart rate and blood pressure, stimulates secretion of adrenaline, and increases blood flow to skeletal muscles, among other effects. The parasympathetic division predominates at times when energy reserves can be conserved and stored for later use; hence this system increases salivation, digestion, and storage of glucose and other nutrients, as well as slowing heart rate and decreasing respiration.
In addition to contrasting functions, the two branches of the ANS have anatomical differences, including points of origin in the CNS. The cell bodies of the efferent sympathetic neurons are in the ventral horn of the spinal cord at the thoracic and lumbar regions. Their axons project for a relatively short distance before they synapse with a cluster of cell bodies called sympathetic ganglia. Some of these ganglia are lined up very close to the spinal cord, while others such as the celiac ganglion are located somewhat farther away. These preganglionic fibers release the neurotransmitter acetylcholine onto the cell bodies in the ganglia. The postganglionic cells project their axons for a relatively long distance to the target tissues, where they release the neurotransmitter norepinephrine.
In contrast, the cell bodies of the efferent parasympathetic neurons are located either in the brain (cranial nerves III, VII, IX, and X) or in the ventral horn of the spinal cord at the sacral region. The preganglionic neurons travel long distances to synapse on cells in the parasympathetic ganglia that are not neatly lined up along the spinal cord but are close to individual target organs. The preganglionic fibers release acetylcholine, just as the sympathetic preganglionics do. However, the parasympathetic postganglionic neurons, which are quite short, also release acetylcholine. Understanding the autonomic nervous system is especially important to psychopharmacologists because many psychotherapeutic drugs alter either norepinephrine or acetylcholine in the brain to relieve symptoms, but by altering those same neurotransmitters in the peripheral nerves, the drugs often produce annoying or dangerous side effects such as elevated blood pressure, dry mouth, or urinary problems (all related to autonomic function).
CNS functioning is dependent on structural features
The tough bone of the skull and vertebrae maintains the integrity of the delicate tissue of the brain and spinal cord. Additionally, three layers of tissue called meninges lie just within the bony covering and provide additional protection. The outermost layer, which is also the toughest, is the dura mater. The arachnoid, just below the dura, is a membrane with a weblike sublayer (subarachnoid space) filled with cerebrospinal fluid (CSF). The brain essentially floats in CSF, so the CSF cushions the organ from trauma and reduces the pressure on the base of the brain. Finally, the pia mater is a thin layer of tissue that sits directly on the nervous tissue.
The CSF not only surrounds the brain but also fills the irregularly shaped cavities within the brain, called cerebral ventricles, and the channel that runs the length of the spinal cord, called the central canal. The CSF is formed by the choroid plexus within the lateral ventricle of each hemisphere and flows to the third and fourth ventricles before moving into the subarachnoid space to bathe the exterior of the brain and spinal cord. CSF not only protects the brain but also helps in the exchange of nutrients and waste products between the brain and the blood. This exchange is possible because the capillaries found in the choroid plexus do not have the tight junctions typical of capillaries in the brain. These tight junctions constitute the blood-brain barrier, a vital mechanism to protect the delicate chemical balance in the CNS.
The CNS has six distinct regions reflecting embryological development
The six anatomical divisions of the adult CNS are evident in the developing embryo. The CNS starts out as a fluid-filled tube that soon develops three enlargements at one end that become the adult hindbrain, midbrain, and forebrain, while the remainder of the neural tube becomes the spinal cord. The fluid-filled chamber itself becomes the ventricular system in the brain and the central canal in the spinal cord. Within 2 months of conception, further subdivisions occur: the hindbrain enlargement develops two swellings, as does the forebrain. These divisions, in ascending order, are the spinal cord, myelencephalon, metencephalon, mesencephalon, diencephalon, and telencephalon. Each region can be further subdivided into clusters of cell bodies, called nuclei, and their associated bundles of axons, called tracts. (In the PNS they are called ganglia and nerves, respectively.) These interconnecting networks of cells will be the focus in much of the remainder of this website, because drugs that alter brain function, that is, psychotropic drugs, modify the interactions of these neurons.
Spinal cord The spinal cord is made up of gray and white matter. The former appears butterfly shaped in cross section (Figure 2.20A) and is called gray matter because the large number of cell bodies in this region appear dark on histological examination. The cell bodies include cell groups that receive information from sensory afferent neurons entering the dorsal horn and cell bodies of motor neurons in the ventral horn that send efferents to skeletal muscles. The white matter surrounding the butterfly-shaped gray matter is made up of myelinated axons of ascending pathways that conduct sensory information to the brain and of descending pathways from higher centers to the motor neurons that initiate muscle contraction.
As we move up the spinal cord and enter the skull, the spinal cord enlarges and becomes the brain stem. If you examine the ventral surface of the brain, the brain stem with its three principal parts, the medulla, pons, and midbrain, is clearly visible. The brain stem contains the reticular formation, a large network of cells and interconnecting fibers that extends up the core of the brain stem for most of its length. Additionally, the brain stem is the origin of numerous cranial nerves that receive sensory information from the skin and joints of the face, head, and neck as well as serving motor control to the muscles in that region. Finally, a significant volume of the brain stem is made up of ascending and descending axons coursing between the spinal cord and higher brain regions. The relationship of the structures of the brain stem is also apparent in the midsagittal view.
Myelencephalon The first major structure of the brain stem we encounter is the myelencephalon, or medulla. Within the medulla, multiple cell groups regulate vital functions including heart rate, digestion, respiration, blood pressure, coughing, and vomiting. When an individual dies from a drug overdose, the cause is most often depression of the respiratory center in the medulla. Also located in the medulla is the area postrema, or vomiting center described in an earlier posts as a cluster of cells with a reduced blood-brain barrier that initiates vomiting in response to toxins in the blood. Drugs in the opiate class such as morphine act on the area postrema and produce vomiting, a common unpleasant side effect of treatment for pain. The nuclei for cranial nerves XI and XII that control the muscles of the neck and tongue are also located in the medulla.
Metencephalon Two large structures within the metencephalon are the pons and cerebellum. Within the central core of the pons and extending rostrally into the midbrain and caudally into the medulla is the reticular formation. The reticular formation is not really a structure but a collection of perhaps 100 small nuclei forming a network that plays an important role in arousal, attention, sleep, and muscle tone, as well as some cardiac and respiratory reflexes. One nucleus called the locus coeruleus is of particular importance to psychopharmacology because it is a cluster of cell bodies that distribute their axons to many areas of the forebrain. These cells are the principal source of all the neurons utilizing the neurotransmitter norepinephrine. When active, these cells cause arousal, increased vigilance, and attention. Drugs like amphetamine enhance their function, causing sleeplessness and enhanced alertness.
Other cell groups within the pons that also belong to the reticular formation are the dorsal and median raphe nuclei. These two clusters of cells are the source of most of the neurons in the CNS that utilize serotonin as their neurotransmitter. Together, the cell bodies in the dorsal and median raphe send axons releasing serotonin to virtually all forebrain areas and function in the regulation of diverse processes including sleep, aggression and impulsiveness, neuroendocrine functions, and emotion. Having a generally inhibitory effect on CNS function, serotonin may maintain behaviors within specific limits. Drugs such as LSD produce their dramatic hallucinogenic effects by inhibiting the inhibitory functions of the raphe nuclei.
The cerebellum is a large foliated structure on the dorsal surface of the brain that connects to the pons by several large bundles of axons called cerebellar peduncles. The cerebellum is a significant sensorimotor center and receives visual, auditory, and somatosensory input as well as information about body position and balance from the vestibular system. By coordinating the sensory information with motor information received from the cerebral cortex, the cerebellum coordinates and smoothes out movements by timing and patterning skeletal muscle contractions. In addition, the cerebellum allows us to make corrective movements to maintain our balance and posture. Damage to the cerebellum produces poor coordination and jerky movements. Drugs such as alcohol at moderate doses inhibit the function of the cerebellum and cause slurred speech and staggering.
Mesencephalon The midbrain has two divisions: the tectum and the tegmentum. The tectum is the dorsal- most structure and consists of the superior colliculi, which are part of the visual system, and the inferior colliculi, which are part of the auditory system. These nuclei are involved in reflexes including the pupillary reflex to light, eye movement, and reactions to moving stimuli.
Within the tegmentum are several structures that are particularly important to psychopharmacologists. The first is the periaqueductal gray (PAG), which surrounds the cerebral aqueduct that connects the third and fourth ventricles. The PAG is one of the areas important for the modulation of pain. Local electrical stimulation of these cells produces analgesia but no change in the ability to detect temperature, touch, or pressure. The PAG is rich in opioid receptors, making it an important site for morphine-induced analgesia. the importance of natural opioid neuropeptides and the PAG in pain regulation. The PAG is also important in sequencing species-specific actions, such as defensive rage and predation.
The substantia nigra is a cluster of cell bodies whose relatively long axons innervate the striatum, a component of the basal ganglia. These cells constitute one of several important neural pathways that utilize dopamine as their neurotransmitter. This pathway is called the nigrostriatal tract. (The names of neural pathways often combine the site of origin of the fibers with their termination site, hence nigrostriatal, meaning substantia nigra to striatum.) This neural circuit is critical for the initiation and modulation of movement. Cell death in the substantia nigra is the cause of Parkinson’s disease, a disorder characterized by tremor, rigidity, and inability to initiate movements. An adjacent cluster of dopaminergic cells in the midbrain is the ventral tegmental area (VTA). Some of these cells project axons to the septum, olfactory tubercle, nucleus accumbens, amygdala, and other limbic structures in the forebrain. Hence these cells form the mesolimbic tract (note that “meso” refers to midbrain). Other cells in the VTA project to structures in the prefrontal cortex, cingulate cortex, and entorhinal areas and are considered the mesocortical tract.
Diencephaion The two major structures in the diencephalon are the thalamus and hypothalamus. The thalamus is a cluster of nuclei that first process and then distribute sensory and motor information to the appropriate portion of the cerebral cortex. For example, the lateral geniculate nucleus of the thalamus receives visual information from the eyes before projecting it to the primary visual cortex. Most of the incoming signals are integrated and modified before being sent on to the cortex. The functioning of the thalamus helps the cortex to direct its attention to selectively important sensory messages while diminishing the significance of others; hence the thalamus helps to regulate levels of awareness.
The second diencephalic structure, the hypothalamus, lies ventral to the thalamus at the base of the brain. Although it is much smaller than the thalamus, it is made up of many small nuclei that perform functions critical to survival. The hypothalamus receives a wide variety of information about the internal environment and, in coordination with closely related structures in the limbic system, initiates various mechanisms important for limiting the variability of the body’s internal states (i.e., they are responsible for homeostasis). Several nuclei are involved in maintaining body temperature and salt-water balance. Other nuclei modulate hunger, thirst, energy metabolism, reproductive behaviors, and emotional responses such as aggression. The hypothalamus directs behaviors for adjusting to these changing needs by controlling both the autonomic nervous system and the endocrine system and organizing behaviors in coordination with other brain areas. Axons from nuclei in the hypothalamus descend into the brain stem to the nuclei of the cranial nerves that provide parasympathetic control. Additionally, other axons descend farther into the spinal cord to influence sympathetic nervous system function. Other hypothalamic nuclei communicate with the contiguous pituitary gland by two methods: neural control of the posterior pituitary and hormonal control of the anterior pituitary By regulating the endocrine hormones, the hypothalamus has widespread and prolonged effects on body physiology. Of particular significance to psychopharmacology is the role of the paraventricular nucleus in regulating the hormonal response to stress, which is involved in clinical depression and anxiety disorders.
Telencephalon The cerebral hemispheres are the largest region of the brain and include the external cerebral cortex, the underlying white matter, and subcortical structures belonging to the basal ganglia and limbic system. The basal ganglia includes the caudate, putamen, and globus pallidus and, along with the substantia nigra in the midbrain, comprises a system for motor control. Drugs to control the symptoms of Parkinson’s disease act on this group of structures.
The limbic system is a complex neural network that is involved in integrating emotional responses and regulating motivated behavior and learning. The limbic system includes the limbic cortex, which is located on the medial and interior surface of the cerebral hemispheres and is transitional between allocortex (phylogenetically older cortex) and neocortex (the more recently evolved six-layer cortex). A significant portion of limbic cortex is the cingulate. the importance of the anterior portion of the cingulate in mediating the emotional component of pain. Some of the significant subcortical limbic structures are the amygdala, nucleus accumbens, and hippocampus, which is connected to the mammillary bodies and the septal nuclei by the fornix, the major tract of the limbic system. The hippocampus is most closely associated with the establishment of new long-term memories and spatial memory and has been the focus of research into Alzheimer’s disease and its treatment. Additionally, the vulnerability of the hippocampus to high levels of stress hormones suggests its involvement in clinical depression and antidepressant drug treatment. The amygdala plays a central role in coordinating the various components of emotional responses, through its profuse connections with the olfactory system, hypothalamus (which is sometimes included in the limbic system even though it is a diencephalic structure), thalamus, hippocampus, striatum, and brain stem nuclei, as well as portions of the neocortex, such as the orbitofrontal cortex. The amygdala and associated limbic areas play a prominent role in our discussions of antidepressants, alcohol, and antianxiety drugs.
The cerebral cortex is divided into four lobes, each having primary, secondary, and tertiary areas
The cerebral cortex is a layer of tissue covering the cerebral hemispheres. In humans, the cortex (or “bark”) is heavily convoluted, having deep grooves called fissures, smaller grooves called sulci, and bulges of tissue between called gyri. Thus the bulge of tissues immediately posterior to the central sulcus is the postcentral gyrus. The convolutions of the cortex greatly enlarge its surface area, to approximately 2.5 square feet. Only about one-third of the surface of the cortex is visible externally, with the remaining two-thirds hidden in the sulci and fissures. There may be as many as 50 to 100 billion cells in the cortex, arranged in six layers horizontal to the surface. Since these layers have large numbers of cell bodies, they appear gray in color; hence they are the gray matter of the cerebral cortex. Each layer can be identified by cell type, size, density, and arrangement. Beneath the six layers, the white matter of the cortex consists of millions of axons that connect one part of the cortex with another or connect cortical cells to other brain structures. One of the largest of these pathways is the corpus callosum, which connects corresponding areas in the two hemispheres. In addition to the horizontal layers, the cortex also has a vertical arrangement of cells that form slender vertical columns running through the entire thickness of the cortex. These vertically oriented cells and their synaptic connections apparently provide the functional units for integration of information between various cortical regions.
The central sulcus and lateral fissure visually divide the cortex into four distinct lobes in each hemisphere: the parietal lobe, occipital lobe, and temporal lobe, all of which are sensory in function, and the frontal lobe, which is responsible for movement and executive planning. Within each lobe is a small primary area, adjacent secondary cortex, and tertiary areas called association cortex. Within the occipital lobe is the primary visual cortex, which receives visual information from the thalamus that originated in the retina of the eye. The primary auditory cortex receives auditory information and is located in the temporal lobe, and the primary somatosensory cortex, which receives information about body senses such as touch, temperature, and pain, is found in the parietal lobe just posterior to the central sulcus. Neither the gustatory cortex, involving taste sensations, nor the primary olfactory area, receiving information regarding the sense of smell, are visible on the surface but lie within the folds of the cortex. The primary cortex of each lobe provides conscious awareness of sensory experience and the initial cortical processing of sensory qualities. Except for olfaction, all sensory information arrives in the appropriate primary cortex via projection neurons from the thalamus. In addition, except for olfaction, sensory information from the left side of the body goes to the right cerebral hemisphere first, and information from the right side goes to the left hemisphere. Visual information is somewhat different in that the left half of the visual field of each eye goes to the right occipital lobe and the right half of the visual field of each eye goes to the left occipital lobe.
Adjacent to each primary area is secondary cortex that consists of neuronal circuits responsible for analyzing the information transmitted from the primary area and providing recognition (or perception) of the stimulus. These areas also are the regions where memories are stored. Farther from the primary areas are association areas that lay down more- complex memories that involve multiple sensory systems such that our memories are not confined to a single sensory system but integrate multiple characteristics of the event. For example, many of us remember pieces of music from the past that automatically evoke visual memories of the person we shared it with or the time in our lives when it was popular. These tertiary association areas are often called the parietal-temporal-occipital association cortex because they represent the interface of the three sensory lobes and provide the higher-order perceptual functions needed for purposeful action.
Within the frontal lobe, the primary motor cortex mediates voluntary movements of the muscles of the limbs and trunk. Neurons originating in primary motor cortex directly, or in several steps, project to the spinal cord to act on spinal motor neurons that end on muscle fibers. As was true for the sensory systems, the motor neurons beginning in the frontal cortex are crossed, meaning that areas of the right primary motor cortex control movements of limbs on the left side of the body and vice versa. Adjacent to the primary motor cortex is the secondary motor cortex, where memories for well- learned motor sequences are stored. Neurons in this area connect directly to the primary motor cortex to direct movement. The rest of the frontal lobe comprises the prefrontal cortex, which receives sensory information from the other cortices via the large bundles of white matter running below the gray matter. Emotional and motivational input is contributed to the prefrontal cortex by limbic and other subcortical structures. The prefrontal cortex is critical for making decisions, planning actions, and evaluating optional strategies. Impaired prefrontal function is characteristic of several psychiatric disorders including borderline personality disorder, memory loss following traumatic brain injury, attention deficit disorder, and others.
The nervous system is made up of the central and peripheral divisions. The CNS includes the brain and spinal cord, and the PNS is made up of the remaining nerves, both spinal and cranial. The PNS is further divided into the somatic nervous system, which includes the mixed spinal nerves that transmit both sensory and motor information to skeletal muscles, and the autonomic nervous system, which serves smooth muscles, glands, and visceral organs. The autonomic nervous system also has two divisions: the sympathetic, which serves to mobilize energy for times of “fight or flight”; and the parasympathetic, which reduces energy utilization and stores reserves. The 12 pairs of cranial nerves perform similar functions for the head and neck.
The CNS can be divided into six regions reflecting embryological development. Within each region are multiple nuclei and their associated axons, which form interconnecting neural circuits that elicit behaviors appropriate to changing conditions. The spinal cord is the first division and has clearly defined regions of gray and white matter when examined in cross section. The gray matter is the cell bodies that receive sensory information and the cell bodies of motor neurons that serve muscles. The white matter is tracts of axons that carry signals in the ascending direction to the brain and descending tracts for cortical control of the spinal cord. Moving rostrally, the spinal cord passes through an opening in the skull and becomes the brain stem. Much of the brain stem also contains the continuation of the axon bundles to and from the spinal cord and, in addition, has clusters of nuclei that can be described on a functional basis.
Continuous with the spinal cord is the myelencephalon, which contains the medulla. This region is populated by multiple nuclei that serve some of the vital functions for survival, such as respiration. The metencephalon includes the cerebellum, which functions to maintain posture and balance and provide fine motor control and coordination. The pons, also part of the metencephalon, contains several nuclei that represent the origins of most of the tracts utilizing the neurotransmitters norepinephrine (the locus coeruleus) and serotonin (the raphe nuclei) in the brain. Beginning in the medulla, running through the pons, and extending into the midbrain is the reticular formation, a network of interconnected nuclei that control arousal, attention, and survival functions. The upper end of the brain stem is the mesencephalon, or midbrain, which contains not only centers that control sensory reflexes such as pupillary constriction but also important sources of neurons (substantia nigra and ventral tegmental area) forming three major dopaminergic tracts. In addition, the periaqueductal gray organizes behaviors such as defensive rage and predation and serves as an important pain-modulating center.
The fifth region is the diencephalon, containing the thalamus, which relays information to the cerebral cortex, and the hypothalamus, which is important for maintaining homeostasis of physiological functions and for modulating motivated behaviors including eating, aggression, reproduction, and so forth. The many nuclei that constitute the hypothalamus control both the autonomic nervous system and the endocrine system.
The telencephalon includes both the cerebral cortex and multiple subcortical structures including the basal ganglia and the limbic system. The basal ganglia modulates movement. The limbic system is made up of several brain structures with perfuse interconnections that modulate emotion, motivation, and learning. Some of the prominent limbic structures are the amygdala, hippocampus, nucleus accumbens, and limbic cortex.
The six-layered cerebral cortex is organized into four lobes: the occipital, temporal, and parietal, which are the sensory lobes involved in perception and memories, and the frontal, which regulates motor movements and contains the “executive mechanism” for planning, evaluating, and making strategies.