Chemical Control of the Brain PDF

CHAPTER FIFTEEN Chemical Control of the Brain and Behavior INTRODUCTION...

CHAPTER FIFTEEN Chemical Control of the Brain and Behavior INTRODUCTION THE SECRETORY HYPOTHALAMUS An Overview of the Hypothalamus Homeostasis Structure and Connections of the Hypothalamus Pathways to the Pituitary Hypothalamic Control of the Posterior Pituitary Hypothalamic Control of the Anterior Pituitary BOX 15.1 OF SPECIAL INTEREST: Stress and the Brain THE AUTONOMIC NERVOUS SYSTEM ANS Circuits Sympathetic and Parasympathetic Divisions The Enteric Division Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Central Control of the ANS Neurotransmitters and the Pharmacology of Autonomic Function Preganglionic Neurotransmitters Postganglionic Neurotransmitters THE DIFFUSE MODULATORY SYSTEMS OF THE BRAIN Anatomy and Functions of the Diffuse Modulatory Systems BOX 15.2 OF SPECIAL INTEREST: You Eat What You Are The Noradrenergic Locus Coeruleus BOX 15.3 PATH OF DISCOVERY: Exploring the Central Noradrenergic Neurons, by Floyd Bloom Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  The Serotonergic Raphe Nuclei The Dopaminergic Substantia Nigra and Ventral Tegmental Area The Cholinergic Basal Forebrain and Brain Stem Complexes Drugs and the Diffuse Modulatory Systems Hallucinogens Stimulants CONCLUDING REMARKS Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  INTRODUCTION It should be obvious by now that knowing the organization of synaptic connections is essential to understanding how the brain works. It’s not from a love of Greek and Latin that we belabor neuroanatomy! Most of the connections we have described are precise and specific. For example, for you to be able to read these words, there must be a very fine-grained neural mapping of the light falling on your retina—how else could you see the dot in this question mark? The information must be carried centrally and dispersed precisely to many parts of the brain for processing, coordinated with control of the motor neurons that closely regulate the six muscles of each eye as it scans the page. In addition to anatomical precision, point-to-point communication in the sensory and motor systems requires mechanisms that restrict synaptic communication to the cleft between the axon terminal and its target. It just wouldn’t do for glutamate released in the somatosensory cortex to activate neurons in the motor cortex! Furthermore, transmission must be brief enough to allow rapid responses to new sensory inputs. Thus, at these synapses, only minute quantities of neurotransmitter are released with each impulse, and these molecules are then quickly destroyed enzymatically or taken up by neighboring cells. The postsynaptic actions at transmitter-gated ion channels last only as long as the transmitter is in the cleft, a few milliseconds at most. Many axon terminals also possess presynaptic “autoreceptors” that detect the transmitter concentrations in the cleft and inhibit release if they get too high. These mechanisms ensure that this type of synaptic transmission is tightly constrained, in both space and time. The elaborate mechanisms that constrain point-to-point synaptic transmission are somewhat like those in telecommunications. Telephone systems make possible very specific connections between one place and another so that your mother in Tacoma can talk just to you in Providence, reminding you that her birthday was last week. The telephone lines or cellular transmissions act like precise synaptic connections. The influence of one neuron (your mother) is targeted to a small number of other Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. neurons (in this case, only you). The embarrassing message is limited to your ears only. The influence of a neuron in one of the sensory or motor systems discussed so far usually extends to the few dozen or few hundred cells it synapses on—a conference call, to be sure, but still relatively specific. Now imagine your mother being interviewed on a television talk show broadcast on a satellite network. The widespread satellite transmission may allow her to tell millions of people that you forgot her birthday, and the loudspeaker in each television set will announce the message to anyone within earshot. Likewise, certain neurons communicate with hundreds of thousands of other cells. These widespread systems tend to act relatively slowly, over seconds to minutes. Because of their broad, protracted actions, such systems in the brain can orchestrate entire behaviors, Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  ranging from falling asleep to falling in love. Indeed, many of the behavioral dysfunctions collectively known as mental disorders are believed to result specifically from imbalances of certain of these chemicals. In this chapter, we look at three components of the nervous system that operate in expanded space and time (Figure 15.1). One component is the secretory hypothalamus. By secreting chemicals directly into the bloodstream, the secretory hypothalamus can influence functions throughout both the brain and the body. A second component, controlled neurally by the hypothalamus, is the autonomic nervous system (ANS), introduced in Chapter 7. Through extensive interconnections within the body, the ANS simultaneously controls the responses of many internal organs, blood vessels, and glands. The third component exists entirely within the central nervous system (CNS) and consists of several related cell groups that differ with respect to the neurotransmitter they use. All of these cell groups extend their spatial reach with highly divergent axonal projections and prolong their actions by using metabotropic postsynaptic receptors. Members of this component of the nervous system are called the diffuse modulatory systems of the brain. The diffuse systems are believed to regulate, among other things, the level of arousal and mood. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  FIGURE 15.1 Patterns of communication in the nervous system. (a) Most of the systems we have discussed in this book may be described as point-to-point. The proper functioning of these systems requires restricted synaptic activation of target cells and signals of brief duration. In contrast, three other components of the nervous system act over great distances and for long periods of time. (b) Neurons of the secretory hypothalamus affect their many targets by releasing hormones directly into the bloodstream. (c) Networks of interconnected neurons of the ANS can work together to activate tissues all over the body. (d) Diffuse modulatory systems extend their reach with widely divergent axonal projections. Description This chapter serves as a general introduction to these systems. Later chapters will explore how they contribute to specific behaviors and brain states: motivation (Chapter 16), sexual behavior (Chapter 17), emotion (Chapter 18), sleep (Chapter 19), and psychiatric disorders (Chapter 22). Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  THE SECRETORY HYPOTHALAMUS Recall from Chapter 7 that the hypothalamus sits below the thalamus, along the walls of the third ventricle. It is connected by a stalk to the pituitary gland, which dangles below the base of the brain, just above the roof of your mouth (Figure 15.2). Although this tiny cluster of nuclei makes up less than 1% of the brain’s mass, the influence of the hypothalamus on body physiology is enormous. Let’s take a brief tour of the hypothalamus and then focus on some of the ways in which it exerts its powerful influence. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  FIGURE 15.2 Locations of the hypothalamus and pituitary. This is a midsagittal section. Notice that the hypothalamus, whose borders are indicated with a dashed line, forms the wall of the third ventricle and sits below the dorsal thalamus. Description An Overview of the Hypothalamus The hypothalamus and dorsal thalamus are adjacent to one another, but their functions are very different. As we saw in the previous seven chapters, the dorsal thalamus lies in the path of all the point-to-point pathways whose destination is the neocortex. Accordingly, the destruction of a small part of the dorsal thalamus can produce a discrete sensory or motor deficit, such as a little blind spot or a lack of feeling on a portion of skin. In contrast, the hypothalamus integrates somatic and visceral responses in accordance with the needs of the brain. A tiny lesion in the hypothalamus can produce dramatic and often fatal disruptions of widely dispersed bodily functions. Homeostasis. In mammals, the requirements for life include a narrow range of body temperatures and blood compositions. The hypothalamus regulates these levels in response to a changing external environment. This regulatory process is called homeostasis, the maintenance of the body’s internal environment within a narrow physiological range. Consider temperature regulation. Biochemical reactions in many cells of the body are fine-tuned to occur at about 37°C. A deviation of more than a few degrees in either direction can be catastrophic. Temperature-sensitive cells in the hypothalamus detect changes in brain temperature and orchestrate the appropriate responses. For example, if you stroll naked through the snow, the hypothalamus issues commands that cause you to shiver (generating heat in the muscles), develop goose bumps (a futile attempt to fluff up your nonexistent fur for better insulation—a reflexive remnant from our hairier ancestors), and turn blue (shunting blood away from cold surface tissues to keep the sensitive core of the body warmer). In contrast, when you go for Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. a jog in the tropics, the hypothalamus activates heat-loss mechanisms that make you turn red (shunting blood to surface tissues where heat can radiate away) and sweat (cooling the skin by evaporation). Other examples of homeostasis are the tight regulation of blood volume, pressure, salinity, acidity, and blood oxygen and glucose concentrations. The means by which the hypothalamus achieves these different types of regulation are remarkably diverse. Structure and Connections of the Hypothalamus. Each side of the hypothalamus has three functional zones: lateral, medial, and periventricular (Figure 15.3). The Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  lateral and medial zones have extensive connections with the brain stem and the telencephalon and regulate certain types of behavior, as we will see in Chapter 16. Here we are concerned only with the third zone, which actually receives much of its input from the other two. FIGURE 15.3 Zones of the hypothalamus. The hypothalamus has three functional zones: lateral, medial, and periventricular. The periventricular zone receives inputs from the other zones, the brain stem, and the telencephalon. Neurosecretory cells in the periventricular zone secrete hormones into the bloodstream. Other periventricular cells control the autonomic nervous system. The periventricular zone is so named because, with the exception of a thin finger of neurons that are displaced laterally by the optic tract (called the supraoptic nucleus), the cells of this region lie right next to the wall of the third ventricle. Within this zone exists a complex mix of neurons with different functions. One group of cells constitutes the suprachiasmatic nucleus (SCN), which lies just above the optic chiasm. These cells receive direct retinal innervation and function to synchronize circadian rhythms with the daily light–dark cycle (see Chapter 19). Other cells in the periventricular zone control the ANS and regulate the outflow of the sympathetic and Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. parasympathetic innervation of the visceral organs. The cells in a third group, called neurosecretory neurons, extend axons down toward the stalk of the pituitary gland. These are the cells that now command our attention. Pathways to the Pituitary We have said that the pituitary dangles below the base of the brain, which is true when the brain is lifted out of the head. In a living brain, however, the pituitary is gently held in a cradle of bone at the base of the skull. It requires this special protection because it is the “mouthpiece” from which much of the hypothalamus “speaks” to the body. The pituitary has two lobes, posterior and anterior. The hypothalamus controls the two lobes in different ways. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  Hypothalamic Control of the Posterior Pituitary. The largest of the hypothalamic neurosecretory cells, magnocellular neurosecretory cells, extend axons down the stalk of the pituitary and into the posterior lobe (Figure 15.4). In the late 1930s, Ernst and Berta Scharrer, working at the University of Frankfurt in Germany, proposed that these neurons release chemical substances directly into the capillaries of the posterior lobe. At the time, this was quite a radical idea. It was well established that chemical messengers called hormones were released by glands into the bloodstream, but no one had thought that a neuron could act like a gland or that a neurotransmitter could act like a hormone. The Scharrers were correct, however. The substances released into the blood by neurons are now called neurohormones. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. FIGURE 15.4 Magnocellular neurosecretory cells of the hypothalamus. This is a midsagittal view of the Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  hypothalamus and pituitary. Magnocellular neurosecretory cells secrete oxytocin and vasopressin directly into capillaries in the posterior lobe of the pituitary. Description The magnocellular neurosecretory cells release two neurohormones into the bloodstream, oxytocin and vasopressin. Both of these chemicals are peptides, each consisting of a chain of nine amino acids. Oxytocin has sometimes been called the “love hormone” because levels rise during sexual or intimate behaviors and promote social bonding (discussed further in Chapter 17). In women, it also plays a critical role during the final stages of childbirth by causing the uterus to contract and facilitating the delivery of the newborn. It also stimulates the ejection of milk from the mammary glands. All lactating mothers know about the complex “letdown” reflex that involves the oxytocin neurons of the hypothalamus. Oxytocin release may be stimulated by the somatic sensations generated by a suckling baby. But the sight or sound of a baby (even someone else’s) can also trigger the release of milk beyond the mother’s conscious control. In each case, information about a sensory stimulus —somatic, visual, or auditory—reaches the cerebral cortex via the usual route, the thalamus, and the cortex ultimately stimulates the hypothalamus to trigger oxytocin release. The cortex can also suppress hypothalamic functions, such as when anxiety inhibits the letdown of milk. Vasopressin, also called antidiuretic hormone (ADH), regulates blood volume and salt concentration. When the body is deprived of water, the blood volume decreases and blood salt concentration increases. These changes are detected by pressure receptors in the cardiovascular system and salt concentration-sensitive cells in the hypothalamus, respectively. Vasopressin-containing neurons receive information about these changes and respond by releasing vasopressin, which acts directly on the kidneys and leads to water retention and reduced urine production. Under conditions of lowered blood volume and pressure, communication between the brain and the kidneys actually occurs in both directions (Figure 15.5). The kidneys secrete an enzyme into the blood called renin. Elevated renin sets off a Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. sequence of biochemical reactions in the blood. Angiotensinogen, a large protein released from the liver, is converted by renin to angiotensin I, which breaks down further to form another small peptide hormone, angiotensin II. Angiotensin II has direct effects on the kidney and blood vessels, which help increase blood pressure. But angiotensin II in the blood is also detected by the subfornical organ, a part of the telencephalon that lacks a blood-brain barrier. Cells in the subfornical organ project axons into the hypothalamus where they activate, among other things, the vasopressin-containing neurosecretory cells. In addition, the subfornical organ activates cells in the lateral area of the hypothalamus, somehow producing an overwhelming thirst that motivates drinking behavior. It may be difficult to accept, but it’s true: To a limited extent, our brain is controlled by our kidneys! This example also Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  illustrates that the means by which the hypothalamus maintains homeostasis go beyond control of the visceral organs and can include behavioral responses. In Chapter 16, we will explore in more detail how the hypothalamus incites behavior. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  FIGURE 15.5 Communication between the kidneys and the brain. Under conditions of lowered blood volume or pressure, the kidney secretes renin into the bloodstream. Renin in the blood promotes the synthesis of the peptide angiotensin II, which excites the neurons in the subfornical organ. The subfornical neurons stimulate the hypothalamus, causing an increase in vasopressin (ADH) production and a feeling of thirst. Description Hypothalamic Control of the Anterior Pituitary. Unlike the posterior lobe, which really is a part of the brain, the anterior lobe of the pituitary is an actual gland. The cells of the anterior lobe synthesize and secrete a wide range of hormones that regulate secretions from other glands throughout the body (together constituting the endocrine system). The pituitary hormones act on the gonads, the thyroid glands, the adrenal glands, and the mammary glands (Table 15.1). For this reason, the anterior pituitary was traditionally described as the body’s “master gland.” But what controls the anterior pituitary? The secretory hypothalamus. The hypothalamus itself is the true master gland of the endocrine system. TABLE 15.1 Hormones of the Anterior Pituitary Hormone Target Action Follicle-stimulating hormone (FSH) Gonads Ovulation, spermatogenesis Luteinizing hormone (LH) Gonads Ovarian and sperm maturation Thyroid-stimulating hormone (TSH); also Thyroid Thyroxin secretion (increases metabolic rate) called thyrotropin Adrenocorticotropic hormone (ACTH); also Adrenal Cortisol secretion (mobilizes energy stores, called corticotropin cortex inhibits immune system, other actions) Growth hormone (GH) All cells Stimulation of protein synthesis Prolactin Mammary Growth and milk secretion glands The anterior lobe is under the control of neurons in the periventricular area called Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. parvocellular neurosecretory cells. These hypothalamic neurons do not extend axons all the way into the anterior lobe; instead, they communicate with their targets via the bloodstream (Figure 15.6). These neurons secrete what are called hypophysiotropic hormones into a uniquely specialized capillary bed at the floor of the third ventricle. These tiny blood vessels run down the stalk of the pituitary and branch in the anterior lobe. This network of blood vessels is called the hypothalamo-pituitary portal circulation. Hypophysiotropic hormones secreted by hypothalamic neurons into the portal circulation travel downstream until they bind to specific receptors on the surface of pituitary cells. Activation of these receptors causes the pituitary cells to either secrete or stop secreting hormones into the general circulation. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. FIGURE 15.6 Parvocellular neurosecretory cells of the hypothalamus. Parvocellular neurosecretory cells secrete hypophysiotropic hormones into specialized capillary beds of the hypothalamo-pituitary portal circulation. These hormones travel to the anterior lobe of the pituitary, where they trigger or inhibit the release of pituitary hormones from secretory cells. Description Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  Regulation of the adrenal glands illustrates how this system works. Located just above the kidneys, the adrenal glands consist of two parts, a shell called the adrenal cortex and a center called the adrenal medulla. The adrenal cortex produces the steroid hormone cortisol; when it is released into the bloodstream, cortisol acts throughout the body to mobilize energy reserves and suppress the immune system, preparing us to carry on in the face of life’s various stresses. In fact, a good stimulus for cortisol release is stress, ranging from physiological stress, such as a loss of blood; to positive emotional stimulation, such as falling in love; to psychological stress, such as anxiety over an upcoming exam. Parvocellular neurosecretory cells that control the adrenal cortex determine whether a stimulus is stressful or not (as defined by the release of cortisol). These neurons lie in the periventricular hypothalamus and release a peptide called corticotropin-releasing hormone (CRH) into the blood of the portal circulation. CRH travels the short distance to the anterior pituitary, where, within about 15 seconds, it stimulates the release of corticotropin, or adrenocorticotropic hormone (ACTH). ACTH enters the general circulation and travels to the adrenal cortex where, within a few minutes, it stimulates cortisol release (Figure 15.7). Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. FIGURE 15.7 The stress response. Under conditions of physiological, emotional, or psychological stimulation or Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  stress, the periventricular hypothalamus secretes corticotropin-releasing hormone (CRH) into the hypothalamo- pituitary portal circulation. This triggers the release of adrenocorticotropic hormone (ACTH) into the general circulation. ACTH stimulates the release of cortisol from the adrenal cortex. Cortisol can act directly on hypothalamic neurons, as well as on other neurons elsewhere in the brain. Description Blood levels of cortisol are, to some extent, self-regulated. Cortisol is a steroid, a class of biochemicals related to cholesterol. Thus, cortisol is a lipophilic (“fat-loving”) molecule, which dissolves easily in lipid membranes and readily crosses the blood- brain barrier. In the brain, cortisol interacts with specific receptors that lead to inhibition of CRH release, thus ensuring that circulating cortisol levels do not get too high. Physicians need to be mindful of this feedback regulation when they prescribe prednisone, a synthetic form of cortisol. Prednisone is a powerful medicine, frequently used to suppress inflammation. When administered for several days, however, the prednisone circulating in the bloodstream fools the brain into thinking that naturally released levels of cortisol are too high and shutting down the release of CRH and the adrenal cortex. Abrupt discontinuation of prednisone treatment does not give the adrenal cortex enough time to ramp up cortisol production and can thus result in what is called adrenal insufficiency. Among the symptoms of adrenal insufficiency are severe abdominal pain and diarrhea, extremely low blood pressure, and changes in mood and personality. Adrenal insufficiency is also a feature of a rare disorder called Addison’s disease, named after Thomas Addison, the British physician who first described the condition in 1849. Addison recognized that one cause of this constellation of symptoms is degeneration of the adrenal gland. Perhaps the most famous sufferer of Addison’s disease was U.S. President John F. Kennedy. Kennedy required a daily regimen of hormone replacement therapy to compensate for the loss of cortisol, a fact that was concealed during his presidency to protect his youthful and vigorous image. The flip side of adrenal insufficiency is a condition called Cushing’s disease, caused by pituitary gland dysfunction that results in elevated levels of ACTH and, Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. consequently, cortisol. The symptoms include rapid weight gain, immune suppression, sleeplessness, memory impairment, and irritability. Not surprisingly, the symptoms of Cushing’s disease are a common side effect of prednisone treatment. The myriad behavioral changes caused by too much (or too little) cortisol may be explained by the fact that neurons with cortisol receptors are found widely distributed in the brain, not just in the hypothalamus. In these other CNS locations, cortisol has been shown to have significant effects on neuronal activity. Thus, we see that the release of hypophysiotropic hormones by cells in the secretory hypothalamus can produce widespread alterations in the physiology of both the body and the brain (Box 15.1). Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  BOX 15.1 OF SPECIAL INTEREST Stress and the Brain Biological stress is created by the brain in response to real or imagined stimuli. The many physiological responses associated with stress help protect the body and the brain from the dangers that triggered the stress in the first place. But stress in chronic doses can have insidious harmful effects as well. Neuroscientists have only begun to understand the relationship between stress, the brain, and brain damage. Stress leads to the release of the steroid hormone cortisol from the adrenal cortex. Cortisol travels to the brain through the bloodstream and binds to receptors in the cytoplasm of many neurons. The activated receptors travel to the cell nucleus, where they stimulate gene transcription and ultimately protein synthesis. One consequence of cortisol’s action is that neurons admit more Ca2+ through voltage-gated ion channels. This may be due to a direct change in the channels, or it may be indirectly caused by changes in the cell’s energy metabolism. Whatever the mechanism, presumably in the short term cortisol makes the brain better able to cope with the stress—perhaps by helping it figure out a way to avoid it! But what about the effects of chronic, unavoidable stress? In Chapter 6, we learned that too much calcium can be a bad thing. If neurons become overloaded with calcium, they die (excitotoxicity). The question naturally arises: Can cortisol kill? Bruce McEwen and his colleagues at Rockefeller University, and Robert Sapolsky and his colleagues at Stanford University, have studied this question in the rat brain. They found that daily injections of corticosterone (rat cortisol) for several weeks caused dendrites to wither in many neurons with corticosterone receptors. A few weeks later, these cells started to die. A similar result was found when, instead of daily hormone injections, the rats were stressed every day. Sapolsky’s studies of baboons in Kenya further reveal the scourges of chronic stress. Baboons in the wild maintain a complex social hierarchy, and subordinate males steer clear of dominant males when they can. During one year when the baboon population boomed, local villagers caged many of the animals to prevent them from destroying their crops. Unable to escape the “top baboons” in the cages, many of the subordinate males subsequently died—not from wounds or malnutrition but apparently from severe and sustained stress-induced effects. They had gastric ulcers, colitis, enlarged adrenal glands, and extensive degeneration of neurons in their hippocampus. Subsequent studies suggest that it is the direct effect of cortisol that damages the hippocampus. These effects of cortisol and stress resemble the effects of aging Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. on the brain. Indeed, research has clearly shown that chronic stress causes premature aging of the brain. In humans, exposure to the horrors of combat, sexual abuse, and other types of extreme violence can lead to posttraumatic stress disorder, with symptoms of heightened anxiety, memory disturbances, and intrusive thoughts. Imaging studies have consistently found degenerative changes in the brains of victims, particularly in the hippocampus. In Chapter 22, we will see that stress, and the brain’s response to it, play a central role in several psychiatric disorders. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  THE AUTONOMIC NERVOUS SYSTEM Besides controlling the ingredients of the hormonal soup that flows in our veins, the periventricular zone of the hypothalamus also controls the autonomic nervous system (ANS). The ANS is an extensive network of interconnected neurons that are widely distributed inside the body. From the Greek autonomia (roughly meaning “independence”), autonomic functions are usually carried out automatically, without conscious, voluntary control. They are also highly coordinated functions. Imagine a sudden crisis. In a morning class, as you are engrossed in a crossword puzzle, the instructor unexpectedly calls you to the blackboard to solve an impossible-looking equation. You are faced with a classic fight-or-flight situation, and your body reacts accordingly, even as your conscious mind frantically considers whether to blunder through it or beg off in humiliation. Your ANS triggers a host of physiological responses, including increased heart rate and blood pressure, depressed digestive functions, and mobilized glucose reserves. These responses are all produced by the sympathetic division of the ANS. Now imagine your relief as the class-ending bell suddenly rings, saving you from acute embarrassment and the instructor’s anger. You settle back into your chair, breathe deeply, and read the clue for 24 down. Within a few minutes, your sympathetic responses decrease to low levels, and the functions of your parasympathetic division crank up again: Your heart rate slows and blood pressure drops, digestive functions work harder on breakfast, and you stop sweating. Notice that you may not have moved out of your chair throughout this unpleasant event. Maybe you didn’t even move your pencil. But your body’s internal workings reacted dramatically. Unlike the somatic motor system, whose alpha motor neurons can rapidly excite skeletal muscles with pinpoint accuracy, the actions of the ANS are typically multiple, widespread, and relatively slow. Therefore, the ANS operates in expanded space and time. In addition, unlike the somatic motor system, which can only excite its peripheral targets, the ANS balances synaptic excitation and inhibition to achieve widely coordinated and graded control. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. ANS Circuits Together, the somatic motor system and the ANS constitute the total neural output of the CNS. The somatic motor system has a single function: It innervates and commands skeletal muscle fibers. The ANS has the complex task of commanding every other tissue and organ in the body that is innervated. Both systems have upper motor neurons in the brain that send commands to lower motor neurons, which actually innervate the target structures outside the nervous system. However, they have some interesting differences (Figure 15.8). The cell bodies of all somatic lower motor neurons lie within the CNS in either the ventral horn of the spinal cord or the brain stem. The cell bodies of all autonomic lower motor neurons lie outside the Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  central nervous system, within cell clusters called autonomic ganglia. The neurons in these ganglia are called postganglionic neurons. Postganglionic neurons are driven by preganglionic neurons, whose cell bodies are in the spinal cord and brain stem. Thus, the somatic motor system controls its targets (skeletal muscles) via a monosynaptic pathway, while the ANS influences its targets (smooth muscles, cardiac muscle, and glands) using a disynaptic pathway. FIGURE 15.8 The organization of the three neural outputs of the CNS. The sole output of the somatic motor Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. system is the lower motor neurons in the ventral horn of the spinal cord and the brain stem, which control skeletal muscle. Visceral functions such as salivating, sweating, and genital stimulation depend on the sympathetic and parasympathetic divisions of the ANS, whose lower motor neurons (i.e., postganglionic neurons) lie outside the CNS in autonomic ganglia. Description Sympathetic and Parasympathetic Divisions. The sympathetic and parasympathetic divisions operate in parallel, but they use pathways that are quite distinct in structure and in their neurotransmitter systems. Preganglionic axons of the sympathetic division emerge only from the middle third of the spinal cord (thoracic Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  and lumbar segments). In contrast, preganglionic axons of the parasympathetic division emerge only from the brain stem and the lowest (sacral) segments of the spinal cord, so the two systems complement each other anatomically (Figure 15.9). Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. FIGURE 15.9 The chemical and anatomical organization of the sympathetic and parasympathetic Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  divisions of the ANS. Notice that the preganglionic inputs of both divisions use ACh as a neurotransmitter. The postganglionic parasympathetic innervation of the visceral organs also uses ACh, but the postganglionic sympathetic innervation uses NE (with the exception of innervation of the sweat glands and vascular smooth muscle within skeletal muscle, which use ACh). The adrenal medulla receives preganglionic sympathetic innervation and secretes epinephrine into the bloodstream when activated. Note the pattern of innervation by the sympathetic division: Target organs in the chest cavity are innervated by postganglionic neurons originating in the sympathetic chain, and target organs in the abdominal cavity are innervated by postganglionic neurons originating in the collateral ganglia. Description The preganglionic neurons of the sympathetic division lie within the intermediolateral gray matter of the spinal cord. They send their axons through the ventral roots to synapse on neurons in the ganglia of the sympathetic chain, which lies next to the spinal column, or within collateral ganglia found within the abdominal cavity. The preganglionic parasympathetic neurons, on the other hand, sit within a variety of brain stem nuclei and the lower (sacral) spinal cord, and their axons travel within several cranial nerves as well as the nerves of the sacral spinal cord. The parasympathetic preganglionic axons travel much farther than the sympathetic axons because the parasympathetic ganglia are typically located next to, on, or in their target organs (see Figures 15.8 and 15.9). The ANS innervates three types of tissue: glands, smooth muscle, and cardiac muscle. Thus, almost every part of the body is a target of the ANS, as shown in Figure 15.9. The ANS: Innervates the secretory glands (salivary, sweat, tear, and various mucus- producing glands). Innervates the heart and blood vessels to control blood pressure and flow. Innervates the bronchi of the lungs to meet the oxygen demands of the body. Regulates the digestive and metabolic functions of the liver, gastrointestinal tract, and pancreas. Regulates the functions of the kidney, urinary bladder, large intestine, and rectum. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Is essential to the sexual responses of the genitals and reproductive organs. Interacts with the body’s immune system. The physiological influences of the sympathetic and parasympathetic divisions generally oppose each other. The sympathetic division tends to be most active during a crisis, real or perceived. The behaviors related to it are summarized in the puerile (but effective) mnemonic used by medical students, called the four Fs: fight, flight, fright, and sex. The parasympathetic division facilitates various non–four-F processes, such as digestion, growth, immune responses, and energy storage. In most cases, the activity levels of the two ANS divisions are reciprocal; when one is high, the other tends to be low, and vice versa. The sympathetic division frenetically Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  mobilizes the body for a short-term emergency at the expense of processes that keep it healthy over the long term. The parasympathetic division works calmly for the long-term good. Both cannot be stimulated strongly at the same time; their general goals are incompatible. Fortunately, neural circuits in the CNS inhibit activity in one division when the other is active. Some examples illustrate how the balance of activity in the sympathetic and parasympathetic divisions controls organ functions. The pacemaker region of the heart triggers each heartbeat without the help of neurons, but both divisions of the ANS innervate it and modulate it; sympathetic activity results in an increase in the rate of beating, while parasympathetic activity slows it down. The smooth muscles of the gastrointestinal tract are also dually innervated, but the effect of each division is the opposite of its effect on the heart. Intestinal motility, and thus digestion, is stimulated by parasympathetic axons and inhibited by sympathetic axons. Not all tissues receive innervation from both divisions of the ANS, however. For example, blood vessels of the skin, and the sweat glands, are innervated (and excited) only by sympathetic axons. Lacrimal (tear-producing) glands are innervated (and excited) only by parasympathetic input. Another example of the balance of parasympathetic–sympathetic activity is the curious neural control of the male sexual response. Erection of the human penis is a hydraulic process. It occurs when the penis becomes engorged with blood, which is triggered and sustained by parasympathetic activity. The curious part is that orgasm and ejaculation are triggered by sympathetic activity. You can imagine how complicated it must be for the nervous system to orchestrate the entire sexual act; parasympathetic activity gets it going (and keeps it going), but a shift to sympathetic activity is necessary to bring it to a successful conclusion. Anxiety and worry, and their attendant sympathetic activity, tend to inhibit erection and promote ejaculation. Not surprisingly, impotence and premature ejaculation are common complaints of the overstressed male. (We will discuss sexual behavior further in Chapter 17.) The Enteric Division. The “little brain,” as the enteric division of the ANS is sometimes called, is a unique neural system embedded in an unlikely place: the Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. lining of the esophagus, stomach, intestines, pancreas, and gallbladder. It consists of two complicated networks, each with sensory nerves, interneurons, and autonomic motor neurons, called the myenteric (Auerbach’s) plexus and submucous (Meissner’s) plexus (Figure 15.10). These networks control many of the physiological processes involved in the transport and digestion of food, from oral to anal openings. The enteric system is not small; it contains about 500 million neurons, the same number of neurons as the entire spinal cord! Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. FIGURE 15.10 The enteric division of the ANS. This cross-sectional view of the small intestine shows the two networks of the enteric division: the myenteric plexus and the submucous plexus. They both contain visceral sensory and motor neurons that control the functions of the digestive organs. Description Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  If the enteric division of the ANS qualifies as “brain” (which may be overstating the case), it is because it can operate with a great deal of independence. Enteric sensory neurons monitor tension and stretch of the gastrointestinal walls, the chemical status of stomach and intestinal contents, and hormone levels in the blood. This information is used by enteric interneuronal circuits and motor neurons, which also reside in the gut, to govern smooth muscle motility, the production of mucous and digestive secretions, and the diameter of the local blood vessels. For example, consider a partially digested pizza making its way through the small intestine. The enteric nervous system ensures that lubricating mucus and digestive enzymes are delivered, that rhythmic (peristaltic) muscle action works to mix the pizza and enzymes thoroughly, and that intestinal blood flow increases to provide a sufficient fluid source and transport newly acquired nutrients to the rest of the body. The enteric division is not entirely autonomous. It receives input indirectly from the “real” brain via axons of the sympathetic and parasympathetic divisions. These provide supplementary control and can supersede the functions of the enteric division in some circumstances. For example, the enteric nervous system and digestive functions are inhibited by the strong activation of the sympathetic nervous system that occurs during acute stress. Central Control of the ANS. As we have said, the hypothalamus is the main regulator of the autonomic preganglionic neurons. Somehow this diminutive structure integrates the diverse information it receives about the body’s status, anticipates some of its needs, and provides a coordinated set of both neural and hormonal outputs. Essential to autonomic control are the connections of the periventricular zone to the brain stem and spinal cord nuclei that contain the preganglionic neurons of the sympathetic and parasympathetic divisions. The nucleus of the solitary tract, located in the medulla and connected with the hypothalamus, is another important center for autonomic control. In fact, some autonomic functions operate well even when the brain stem is disconnected from all structures above it, including the hypothalamus. The solitary nucleus integrates sensory information from the internal organs and coordinates output to the autonomic brain stem nuclei. Copyright © 2020. Jones & Bartlett Learning, LLC. All rights reserved. Neurotransmitters and the Pharmacology of Autonomic Function Even people who have never heard the word neurotransmitter know what it means to “get your adrenaline flowing.” (In the United Kingdom, this compound is called adrenaline, while in the United States, it is called epinephrine.) Historically, the autonomic nervous system has probably taught us more than any other part of the body about how neurotransmitters work. Because the ANS is relatively simple compared to the CNS, we understand the ANS much better. In addition, neurons of the peripheral parts of the ANS are outside the blood-brain barrier, so all drugs that enter the bloodstream have direct access to them. The relative simplicity and Bear, Mark, et al. Neuroscience: Exploring the Brain, Enhanced Edition : Exploring the Brain, Enhanced Edition, Jones & Bartlett Learning, LLC, 2020. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/berkeley-ebooks/detail.action?docID=6175387. Created from berkeley-ebooks on 2024-09-09 09:35:47.  accessibility of the ANS have led to a deeper understanding of the mechanisms of drugs that influence synaptic transmission. Preganglionic Neurotransmitters. The primary transmitter of the peripheral autonomic neurons is acetylcholine (ACh), the same transmitter used at skeletal neuromuscular junctions. The preganglionic neurons of both sympathetic and parasympathetic divisions release ACh. The immediate effect is that the ACh binds to nicotinic ACh receptors (nAChR), which are ACh-gated channels, and evokes a fast excitatory postsynaptic potential (EPSP) that usually triggers an action potential in the postganglionic cell.