Fisiologia e Comportamento, Resumos de Fisiologia

Baixe Fisiologia e Comportamento e outras Resumos em PDF para Fisiologia, somente na Docsity! Structure and Functions of Cells of the Nervous System Neurons Supporting Cells The Blood-Brain Barrier Section Summary Neural Communication: An Overview Measuring Electrical Potentials of Axons The Membrane Potential: Balance of Two Forces The Action Potential Conduction of the Action Potential Section Summary Structure of Synapses Release of Neurotransmitter Activation of Receptors Postsynaptic Potentials Termination of Postsynaptic Potentials Effects of Postsynaptic Potentials: Neural Integration Autoreceptors Other Types of Synapses Nonsynaptic Chemical Communication Section Summary Kathryn D. was getting desperate. AIl her life she had been healthy and active, eating wisely and keeping fit with sports and regular exercise. She went to her health club almost every day for a session of low-impact aerobies followed by a swim. But several months ago she began having trouble keeping up with her usual schedule. At first, she found herself getting tired toward the end of her aerobics class. Her arms, particularly, seemed to get heavy. Then when she entered the pool and started swimming, she found that it was hard to lift her arms over her head; she abandoned the crawl and the backstroke and did the sidestroke and breaststroke instead. She did not have any flulike symptoms, so she told herself that she needed more sleep and perhaps she should eat a little more. Over the next few weeks, however, things only got worse. Aerobics classes were becoming an ordeal. Her instructor became concerned and suggested that Kathryn see her doctor. She did so, but he could find nothing wrong with her. She was not anemic, showed no signs of an infection, and seemed to be well nourished. He asked how things were going at work. “Well, lately I've been under some pressure,” she said. "The head of my department quit a few weeks ago, and I've taken over his job temporarily. | think | have a chance of getting the job permanentiy, but | feel as ifmy bosses are watching me to see whether I'm good enough for the job.” Kathryn and her physician agreed that increased stress could be the cause of her problem. "I'd prefer not to give you any medication at this time,” he said, “but if you don't feel better soon we'll have a closer look at you.” She did feel better for a while, but then all of a sudden her symptoms got worse. She quit going to the health club and found that she even had difficulty finishing a day's work. Il we can do—perceive, think, learn, remember, act—is made possible by the integrated activity of the cells of the nervous system. This chapter describes the structure and functions of these cells. Information, in the form of light, sound waves, odors, tastes, or contact with objects, is gathered from the envi- ronment by specialized cells called sensory neurons. Movements are accomplished by the contraction of muscles, which are controlled by motor neurons. (The term motor is used here in its original sense to refer to movement, not to a mechanical engine.) And in be- tween sensory neurons and motor neurons come the interneurons—neurons that lie entirely within the She was certain that people were noticing that she was no longer her lively self, and she was afraid that her chances for the promotion were slipping away. One afternoon she tried to look up at the clock on the wall and realized that she could hardly see—her eyelids were drooping, and her head fekt as if it weighed a hundred pounds. Just then, one of her supervisors came over to her desk, sat down, and asked her to fill him in on the progress she had been making on a new project. As she talked, she found herself getting weaker and weaker. Her jaw was getting tired, even her tongue was getting tired, and her voice was getting weaker. With a sudden feeling of fright she realized that the act of breathing seemed to take a lot of effort. She managed to finish the interview, but immediately afterward she packed up her briefcase and left for home, saying that she had a bad headache. She telephoned her physician, who immediately arranged for her to go to the hospital to be seen by Dr. T., a neurologist. Dr. T. listened to a description of Kathryn's symptoms and examined her briefly. She said to Kathryn, “L think | know what may be causing your symptoms. I'd like to give you an injection and watch your reaction.” She gave some orders to the nurse, who left the room and came back with a syringe. Dr. T. took it, swabbed Kathryn's arm, and injected the drug. She started questioning Kathryn about her job. Kathryn answered slowly, her voice almost a whisper. As the questions continued, she realized that it was getting easier and easier to talk. She straight- ened her back and took a deep breath. Yes, she was sure. Her strength was returning! She stood up and raised her arms above her head. “Look,” she said, her excitement growing. “I can do this again. I've got my strength back! What was that you gave me? Am | cured?” (For an answer to her question, see p. 59.) central nervous system. Local intemeurons form circuits with nearby neurons and analyze small pieces of infor- mation. Relay interneurons connect circuits of local inter- neurons in one region of the brain with those in other [> sensory neuron A neuron that detects changes in the external or internal environment and sends information about these changes to the central nervous system. > motor neuron A neuron located within the central nervous system that controls the contraction of a muscle or the secretion of a gland. [> interneuron A neuron located entirely within the central nervous system.  FIGURE 2.3 Nerves A nerve consists of a sheath of tissue that encases a bundle of individual nerve fibers (also known as axons). BV = blood vessel; A = individual axons. (From Tissues and Organs: A Text-Atlas of Scanning Electron Microscopy, by Richard G. Kessel and Randy H. Kardon. Copyright O 1979 by W. H. Freeman and Co. Reprinted by permission of Barbara Kessel and Randy Kardon.) prefer the original French word bouton, and others sim- ply refer to them as terminais.) Terminal buttons have a very special function: When an action potential traveling down the axon reaches them, they secrete a chemical called a neurotransmitter. This chemical (there are many different ones in the CNS) either excites or inhibits the Synapse on soma Cell body Synapse on dendrite Cells of the Nervous System 31 receiving cell and thus helps to determine whether an action potential occurs in its axon. Details of this process will be described later in this chapter. An individual neuron receives information from the terminal buttons of axons of other neurons—and the terminal buttons of its axons form synapses with other neurons. A neuron may receive information from dozens or even hundreds of other neurons, each of which can form a large number of synaptic connections with it. Figure 2.4 illustrates the nature of these connections. As you can see, terminal buttons can form synapses on the membrane of the dendrites or the soma. (See Figure 2.4.) INTERNAL STRUCTURE Figure 2.5 illustrates the internal structure ofa typical mul- tipolar neuron. (See Figure 2.5.) The membrane defines the boundary of the cell. It consists of a double layer of lipid (fauike) molecules. Embedded in the membrane are a variety of protein molecules that have special functions. Some proteins detect substances outside the cell (such as hormones) and pass information about the presence of these substances to the interior of the cell. Other proteins > neurotransmitter A chemical that is released by a terminal button; has an excitatory or inhibitory effect on another neuron. > membrane A structure consisting principally of lipid molecules that defines the outer boundaries of a cell and also constitutes many of the cell organelles, such as the Golgi apparatus. FIGURE 2.4 An Overview of the Synaptic Connections Between Neurons The arrows represent the directions of the flow of information. 32 Chapter 2 Structure and Functions of Cells of the Nervous System Dendritic Membrane Microtubules Myelin sheath FIGURE 2.5 The Principal Internal Structures of a Multipolar Neuron control access to the interior of the cell, permitting some substances to enter but barring others. Still other proteins act as transporters, actively carrying certain molecules into or out of the cell. Because the proteins that are found in the membrane of the neuron are especially important in the transmission of information, their characteristics will be discussed in more detail later in this chapter. The nucleus (“nut”) of the cell is round or oval and is enclosed by the nuclear membrane. The nucleolus and the chromosomes reside here. The nucleolus is responsible for the production of ribosomes, small struc- tures that are involved in protein synthesis. The chromo- somes, which consist of long strands of deoxyribonucleic acid (DNA), contain the organism's genetic informa- tion. When they are active, portions of the chromosomes (genes) cause production of another complex molecule, messenger ribonucleic acid (mRNA), which receives a copy of the information stored at that location. The mRNA leaves the nuclear membrane and attaches to ri- bosomes, where it causes the production of a particular protein. (See Figure 2.6.) Proteins are important in cell functions. As well as providing structure, proteins serve as enzymes, which direct the chemical processes of a cell by controlling chemical reactions. Enzymes are special protein mole- cules that act as catalysts; that is, they cause a chemical reaction to take place without becoming a part of the final product themselves. Because cells contain the ingre- dients needed to synthesize an enormous variety of com- pounds, the ones that cells actually do produce depend primarily on the particular enzymes that are present. Furthermore, there are enzymes that break molecules apart as well as enzymes that put them together; the en- zymes that are present in a particular region ofa cell thus determine which molecules remain intact. For example, x o A+ BSAB e Y In this reversible reaction the relative concentrations of enzymes X and Y determine whether the complex substance AB or its constituents, A and B, will predominate. [> nucleus A structure in the central region of a cell, containin: the nucleolus and chromosomes. [> nucleolus (new clee o lus) A structure within the nucleus of a cell that produces the ribosomes. [> ribosome (ry bo soam) A cytoplasmic structure, made of protein, that serves as the site of production of proteins translated from mRNA. > chromosome A strand of DNA, with associated proteins, found in the nucleus; carries genetic information. [> deoxyribonudleic acid (DNA) (dee ox ce ry bo new clayik) Along, complex macromolecule consisting of two interconnected helical strands; along with associated proteins, strands of DNA constitute the chromosomes. > gene The functional unit of the chromosome, which directs synthesis of one or more proteins. [> messenger ribonucleic acid (mRNA) A macromolecule that delivers genetic information concerning the synthesis of a protein from a portion of a chromosome to a ribosome. [> enzyme A molecule that controls a chemical reaction, combining two substances or breaking a substance into two parts. Cells of the Nervous System 33 Detail of Nucleus FIGURE 2.6 Protein Synthesis When a gene is active, a copy of the information is made onto a molecule of messenger RNA. The mRNA leaves the nucleus and attaches to a ribosome, where the protein is produced. Enzyme X makes A and B join together; enzyme Y splits AB apart. (Energy may also be required to make the reac- tions proceed.) As you undoubtedly know, the sequence of the hu- man genome-—along with that of several other plants and animals—has been determined. (The genome is the se- quence of nucleotide bases on the chromosomes that provide the information needed to synthesize all the pro- teins that can be produced by a particular organism.) Bi- ologists were surpriscd to learn that the number of genes was not correlated with the complexity of the organism (Mattick, 2004). For example, Caenorhabditis elegans, a simple worm that consists of about 1000 cells, has 19,000 genes, whereas humans have around 25,000 genes. The research also revealed that the genomes of most verte- brates contained much “junk” DNA, which did not con- tain information needed to produce proteins. For exam- ple, only about 1.5 percent of the human genome encodes for proteins. At first, molecular geneticists assumed that “junk” DNA was a leftover from our evolutionary history and that only the sequences of DNA that encoded for proteins were useful. However, further research found that the amount of non-protein-coding DNA did corre- late well with the complexity of an organism and that many of these sequences have been conserved for mil- lions of years. In other words, it started looking as though “junk” DNA was not junk after all. (See Figure 2.7.) A study by Woolfe etal. (2005) illustrates the longevity of most non-coding DNA. The researchers compared the genomes of the human and the pufferfish. The common ancestor of these two species lived many millions of years ago, which means that if non-coding DNA is really just useless, leftover junk, then random mutations should a Percent of DNA not coding for protein E É SS sê e SA a E 9 FIGURE 2.7 Non-coding DNA This figure shows the percentage of DNA that does not code for proteins in various categories of living organisms. (Adapted from Mattick, 1. S. Scientific American, 2004, 291, 60-67.) 36 Chapter 2 Structure and Functions of Cells of the Nervous System carries substances from the terminal buttons to the soma, a process known as retrograde axoplasmic trans- port. Anterograde axoplasmic transport is remarkably fast: up to 500 mm per day. Retrograde axoplasmic transport is about half as fast as anterograde transport. Supporting Cells Neurons constitute only about half the volume of the CNS. The rest consists of a variety of supporting cells. Because neurons have a very high rate of metabolism but have no means of storing nutrients, they must con- stantly be supplied with nutrients and oxygen or they will quickly die. Thus, the role played by the cells that support and protect neurons is very important to our existence. GLIA The most important supporting cells of the central nervous system are the neuroglia, or “nerve glue.” Glia (also called glial cells) do indeed glue the CNS to- gether, but they do much more than that. Neurons lead a very sheltered existence; they are buffered phys- ically and chemically from the rest of the body by the glial cells. Glial cells surround neurons and hold them in place, controlling their supply of nutrients and some of the chemicals they need to exchange mes- sages with other neurons; they insulate neurons from one another so that neural messages do not get scram- bled; and they even act as housekcepers, destroying and removing the carcasses of neurons that are killed by disease or injury. There are several types of glial cells, each of which plays a special role in the CNS. The three most impor- tant types are astrocytes, oligodendrocytes, and microglia. Astrocyte means “star cell,” and this name accurately describes the shape of these cells. Astrocytes provide physical support to neurons and clean up debris within the brain. They produce some chemicals that neurons need to fulfill their functions. They help to control the chemical composition of the fluid surrounding neu- rons by actively taking up or releasing substances whose concentrations must be kept within critical levels. Fi- nally, astrocytes are involved in providing nourishment to neurons. Some of the astrocyte's processes (the arms of the star) are wrapped around blood vessels; other processes are wrapped around parts of neurons, so the somatic and dendritic membranes of neurons are largely sur- rounded by astrocytes. This arrangement suggested to the Italian histologist Camillo Golgi (1844-1926) that astrocytes supplied neurons with nutrients from the capillaries and disposed of their waste products (Golgi, 1903). He thought that nutrients passed from capillaries to the cytoplasm of the astrocytes and then through the cytoplasm to the neurons. Recent evidence suggests that Golgi was right: Al though neurons receive some glucose directly from capillaries, they receive most of their nutrients from astrocytes. Astrocytes receive glucose from capillaries and break it down to lactate, the chemical produced during the first step of glucose metabolism. They then release lactate into the extracellular fluid that surrounds neurons, and neurons take up the lactate, transport it to their mitochondria, and use it for en- ergy (Tsacopoulos and Magistretti, 1996; Brown, Tek- kók, and Ransom, 2003; Pellerin et al., 2007). Appar- ently, this process provides neurons with a fuel that they can metabolize even more rapidly than glucose. In addition, astrocytes store a small amount of a car- bohydrate called glycogen that can be broken down to glucose and then to lactate when the metabolic rate of neurons in their vicinity is especially high. (See Figure 2.9.) Besides transporting chemicals to neurons, astro- cytes serve as the matrix that holds neurons in place— the “nerve glue,” so to speak. These cells also sur- round and isolate synapses, limiting the dispersion of neurotransmitters that are released by the terminal buttons. When cells in the central nervous system die, certain kinds of astrocytes take up the task of cleaning away the debris. These cells are able to travel around the CNS; they extend and retract their processes (pseudopodia, or “false feet”) and glide about the way amoebas do. When these astrocytes contact a piece of debris from a dead neuron, they push themselves against it, finally engulf ing and digesting it. We call this process phagocytosis (phagein, “to eat”; kutos, “cel]). If there is a considerable amount ofinjured tissue to be cleaned up, astrocytes will divide and produce enough new cells to do the task. Once the dead tissue has been broken down, a frame- work of astrocytes will be left to fill in the vacant arca, and a specialized kind of astrocyte will form scar tissue, walling off the area. [> retrograde | In a direction along an axon from the terminal buttons toward the cell body. [> glia (glee ah) The supporting cells of the central nervous system. >> astrocyte A glial cell that provides support for neurons of the central nervous system, provides nutrients and other substances, and regulates the chemical composition of the extracelular fluid. >> phagocytosis (fagg o sy toe sis) The process by which cells engulf and digest other cells or debris caused by cellular degeneration.. >> oligodendroeyte (oh li go den droh site) A type of glial cellin the central nervous system that forms myelin sheaths. Cells of the Nervous System 37 FIGURE 2.9 Structure and Location of Astrocytes The processes of astrocytes surround capillaries and neurons of the central nervous system. The principal function of oligodendrocytes is to provide support to axons and to produce the myelin sheath, which insulates most axons from one an- other. (Very small axons are not myelinated and lack this sheath.) Myelin, 80 percent lipid and 20 percent Myelinated axons Soma of oligodendrocyte Microtubule Mitochondrion in axoplasm Node of Ranvier rigurE 2.10 Oligodendrocyte An oligodendrocyte forms the myelin that surrounds many axons in the central nervous system. Each cell forms one segment of myelin for several adjacent axons. protein, is produced by the oligodendrocytes in the form of a tube surrounding the axon. This tube does not form a continuous sheath; rather, it consists of a series of segments, cach approximately 1 mm long, with a small (1-2 pm) portion of uncoated axon be- tween the segments. (A micrometer, abbreviated pm, is one-millionth of a meter, or one-thousandth of a mil- limeter.) The bare portion of axon is called a node of Ranvier, after the person who discovered it. The myelinated axon, then, resembles a string of elon- gated beads. (Actually, the beads are very much elon- gated—their length is approximately 80 times their width.) A given oligodendrocyte produces up to fifty seg- ments of myelin. During the development of the CNS, oligodendrocytes form processes shaped something like canoe paddles. Each of these paddle-shaped pro- cesses then wraps itself many times around a segment of an axon and, while doing so, produces layers of myelin. Each paddle thus becomes a segment of an axon”s my- elin sheath. (See Figures 2.10 and 2.Ila.) > myelin sheath (my a lin) A sheath that surrounds axons and insulates them, preventing messages from spreading between adjacent axons. > node of Ranvier (raw vee ay) A naked portion of a myelinated axon between adiacent oligodendroglia or Schwann cells. 38 Chapter 2 Structure and Functions of Cells of the Nervous System Axons Myelinsheath (a) Schwamn cell o — —> e (b) FIGURE 2.11 Formation of Myelin During development a process of an oligodendrocyte or an entire Schwann cell tightly wraps itself many times around an individual axon and forms one segment of the myelin sheath. (a) Oligodendrocyte. (b) Schwann cell. Dr. C., a retired neurologist, had been afflicted with multiple sclerosis for more than two decades when she died of a heart attack. One evening, twenty-three years previously, she and her husband had had dinner at their favorite restaurant. As they were leaving, she stumbled and almost fell. Her husband joked, “Hey, honey, you shouldn't have had that last glass of wine.” She smiled at his attempt at humor, but she knew better-—her clumsiness wasn't brought on by the two glasses of wine she had drunk with dinner. She suddently realized that she had been ignoring some symptoms that she should have recognized. The next day, she consulted with one of her col- leagues, who agreed that her own tentative diagnosis was probably correct: Her symptoms fit those of multiple sclerosis. She had experienced fleeting problems with double vision, she sometimes felt unsteady on her feet, and she occasionally noticed tingling sensations in her right hand. None of these symptoms was serious, and they lasted for only a short while, so she ignored them— or perhaps denied to herself that they were important. A few weeks after Dr. C.'s death twenty-three years later, a group of medical students and neurological resi- dents gathered in an autopsy room at the medical school. Dr. D., the school's neuropathologist, displayed a stainless-steel tray on which were lying a brain and a spinal cord. "These belonged to Dr. C.,” he said. “Several years ago she donated her organs to the medi- cal school.” Everyone looked at the brain more intently, knowing that it had animated an esteemed clinician and teacher whom they all knew by reputation, if not person- ally. Dr. D. led his audience to a set of light boxes on the wall, to which several MRI scans had been clipped. He pointed out some white spots that appeared on one scan. “This scan clearly shows some white-matter lesions, but they are gone on the next one, taken six months later. And here is another one, but it's gone on the next scan. The immune system attacked the myelin sheaths in a particular region, and then glial cells cleaned up the debris. MRI doesn't show the lesions then, but the axons can no longer conduct their messages.” He put on a pair of surgical gloves, picked up Dr. C.'s brain, and cut it in several slices. He picked one up. “Here, see this?” He pointed out a spot of discoloration in a band of white matter. "This is a sclerotic plaque—a patch that feels harder than the surrounding tissue. There are many of them, located throughout the brain and spinal cord, which is why the disease is called multiple sclerosis.” He picked up the spinal cord, felt along its length with his thumb and forefinger, and then stopped and said, “Yes, | can feel a plaque right here.” Dr. D. put the spinal cord down and said, “Who can tell me the etiology of this disorder?” One of the students spoke up. “It's an autoimmune disease. The immune system gets sensitized to the body's own myelin protein and periodically attacks it, causing a variety of different neurological symptoms. Some say that a childhood viral illness somehow causes the immune sys- tem to start seeing the protein as foreign.” “That's right,” said Dr. D. “The primary criterion for the diagnosis of multiple sclerosis is the presence of neurological symptoms disseminated in time and space. The symptoms don't all occur at once, and they can be caused only by damage to several different parts of the nervous system, which means that they can't be the result of a stroke.” As their name indicates, microglia are the smallest of the glial cells. Like some types of astrocytes, they act as phagocytes, engulfing and breaking down dead and dying neurons. But, in addition, they serve as one of the representatives of the immune system in the brain, protecting the brain from invading microorganisms. fibers, which compose the cytoskeleton and help to transport chemicals from place to place; and the mitochondria, which serve as the location for most of the chemical reactions through which the cell extracts energy from nutrients. Recent evidence indicates that only a small proportion of the human genome is devoted to the production of protein; the rest (formerly called “junk” DNA) is involved in the production of non-coding RNA, which has a variety of functions. Neurons are supported by the glial cells of the central nervous system and the supporting cells of the peripheral nervous system. In the CNS, astrocytes provide support and nourishment, regulate the com- position of the fluid that surrounds neurons, and remove debris and form scar tissue in the event of tissue damage. Microglia are phagocytes that serve as the representatives of the immune system. Oligodendrocytes form myelin, the substance that insulates axons, and also support unmyelinated axons. In the PNS, support and myelin are provided by the Schwann cells. Communication Within a Neuron This tion describes the nature of communication within a neuron—the way an action potential is sent from the cell body down the axon to the terminal but- tons, informing them to release some neurotransmitter. The details of synaptic transmission—the communica- tion between neurons—will be described in the next section. As we will see in this section, an action potential consists of a series of alterations in the membrane of the axon that permit various substances to move between the interior of the axon and the fluid surrounding it. These exchanges produce electrical currents. To see an interactive animation of the information presented in the following section, (O Simulate the action potential on MyPsychLab. Neural Communication: An Overview Before I begin my discussion of the action potential, let's step back and see how neurons can interact to produce a useful behavior. We begin by examining a simple as- sembly of three neurons and a muscle that control a Communication Within a Neuron 41 In most organs, molecules freely diffuse between the blood within the capillaries that serve them and the extracellular fluid that bathes their cells. The molecules pass through gaps between the cells that line the cap- illaries. The walls of the capillaries of the CNS lack these gaps; conseguently, fewer substances can enter or leave the brain across the blood-brain barrier. m THOUGHT QUESTION The fact that the mitochondria in our cells were orig- inally microorganisms that infected our very remote ancestors points out that evolution can involve inter- actions between two or more species. Many species have other organisms living inside them; in fact, the bacteria in our intestines are necessary for our good health. Some microorganisms can exchange genetic information, so adaptive mutations that develop in one species can be adopted by another. Is it possi- ble that some of the features of the cells of our ner- vous system were bequeathed to our ancestors by other species? withdrawal reflex. In the next two figures (and in subse- quent figures that illustrate simple neural circuits), mul- tipolar neurons are depicted in shorthand fashion as several-sided stars. The points of these stars represent dendrites, and only one or two terminal buttons are shown at the end of the axon. The sensory neuron in this example detects painful stimuli. When its dendrites are stimulated by a noxious stimulus (such as contact with a hot object), it sends messages down the axon to the ter- minal buttons, which are located in the spinal cord. (You will recognize this cell as a unipolar neuron; see Figure 2.13.) The terminal buttons of the sensory neuron re- lease a neurotransmitter that excites the interneuron, causing it to send messages down its axon. The terminal buttons of the interneuron release a neurotransmitter that excites the motor neuron, which sends messages down its axon. The axon of the motor neuron joins a nerve and travels to a muscle. When the terminal buttons of the motor neuron release their neurotransmitter, the muscle cells contract, causing the hand to move away from the hot object. (Look again at Figure 2.13.) So far, all of the synapses have had excitatory effecis. Now let us complicate matters a bit to see the effect of inhibitory synapses. Suppose you have removed a hot casserole from the oven. As you start walking over to the table to put it down, the heat begins to penetrate the 42 Chapter 2 Structure and Functions of Cells of the Nervous System riGURE 2.13 A Withdrawal Reflex Ra Cross section of spinal cord This interneuron excites motor neuron, causing muscular contraction This muscle causes withdrawal from source of pain Dendrites of sensory neuron detect paintul stimulus Axon of sensory neuron (pain) The figure shows a simple example of a useful function of the nervous system. The painful stimulus causes the hand to pull away from the hot iron. rather thin potholders you are using. The pain caused by the heat triggers a withdrawal reflex that tends to make you drop the casserole. Yet you manage to keep hold of it long enough to get to the table and put it down. What prevented your withdrawal reflex from mak- ing you drop the casserole on the floor? The pain from the hot casserole increases the activity of excitatory synapses on the motor neurons, which tends to cause the hand to pull away from the casserole. How- ever, this excitation is counteracted by inhibition, supplied by another source: the brain. The brain contains neural circuits that recognize what a disaster it would be if you dropped the casserole on the floor. These neural circuits send information to the spinal cord that prevents the withdrawal reflex from making you drop the dish. Neuron in brain Brain Axon of neuron in brain Spinal cord Figure 2.14 shows how this information reaches the spinal cord. As you can see, an axon from a neuron in the brain reaches the spinal cord, where its terminal but- tons form synapscs with an inhibitory interncuron. When the neuron in the brain becomes active, its termi- nal buttons excite this inhibitory interneuron. The inter- neuron releases an inhibitory neurotransmitter, which decreases the activity of the motor neuron, blocking the withdrawal reflex. This circuit provides an example of a contest between two competing tendencies: to drop the casserole and to hold onto it. (See Figure 2.14.) Of course, reflexes are more complicated than this description, and the mechanisms that inhibit them are even more so. And thousands of neurons are involved in this process. The five neurons shown in Figure 2.14 This interneuron excites motor neuron, causing muscular contraction This muscle causes withdrawal from source of pain Axon from 4 — neuron in brain Axon of sensory neuron (pain) Cross section of spinal cord This interneuron inhibits. motor neuron, preventing muscular contraction al rIGURE 2.14 The Role of Inhibition Inhibitory signals arising from the brain can prevent the withdrawal reflex from causing the person to drop the casserole. represent many others: Dozens of sensory neurons de- tect the hot object, hundreds of interneurons are stimu- lated by their activity, hundreds of motor neurons pro- duce the contraction—and thousands of neurons in the brain must become active if the reflex is to be inhibited. Yet this simple model provides an overview of the pro- cess of neural communication, which is described in more detail later in this chapter. Measuring Electrical Potentials of Axons Let's examine the nature of the message that is con- ducted along the axon. To do so, we obtain an axon that is large enough to work with. Fortunately, nature has provided the neuroscientist with the giant squid axon (the giant axon of a squid, not the axon of a giant squid!). This axon is about 0.5 mm in diameter, which is hundreds of times larger than the largest mammalian axon. (This large axon controls an emergency response: sudden contraction of the mantle, which squirts water through a jet and propels the squid away from a source of danger.) We place an isolated giant squid axon in a dish of seawater, in which it can exist for a day or two. To measure the electrical charges generated by an axon, we will need to use a pair of electrodes. Electrodes are electrical conductors that provide a path for electric- ity to enter or leave a medium. One of the electrodes is a simple wire that we place in the scawater. The other one, which we use to record the message from the axon, has to be special. Because even a giant squid axon is rather small, we must use a tiny electrode that will re- cord the membrane potential without damaging the axon. To do so, we use a microelectrode. A microelectrode is simply a very small clectrode, which can be made of metal or glass. In this case we will use one made of thin glass tubing, which is heated and drawn down to an exceedingly fine point, less than a thousandth of a millimeter in diameter. Because glass will not conduct electricity, the glass microelectrode is filled with a liquid that conducts electricity, such as a solution of potassium chloride. We place the wire electrode in the seawater and in- sert the microelectrode into the axon. (See Figure 2.15a.) As soon as we do so, we discover that the inside of the axon is negatively charged with respect to the outside; the difference in charge being 70 mV (milli- volts, or thousandths of a volt). Thus, the inside of the membrane is -70 mV. This electrical charge is called the membrane potential. The term potential refers to a stored-up source of energy—in this case, clectrical energy. For example, a flashlight battery that is not con- nected to an electrical circuit has a potential charge of 1.5 V between its terminals. If we connect a light bulb to the terminals, the potential energy is tapped and Communication Within a Neuron 43 Voltmeter Glass microelectrode filled with liquid that conducts electricity Wire electrode placed in seawater —M- Battery (b) (a) rigurE 2.15 Measuring Electrical Charge The figure shows (a) a voltmeter detecting the charge across a membrane of an axon and (b) a light bulb detecting the charge across the terminals of a battery. converted into radiant energy (light). (See Figure 2.15b.) Similarly, if we connect our electrodes—one inside the axon and one outside it—to a very sensitive voltmeter, we will convert the potential energy to movement of the meter's needle. Of course, the potential electrical en- ergy of the axonal membrane is very weak in compari- son with that of a flashlight battery. As we will see, the message that is conducted down the axon consists of a brief change in the membrane potential. However, this change occurs very rapidly—too rapidly for us to sec if we were using a voltmeter. There- fore, to study the message, we will use an oscilloscope. This device, like a voltmeter, measures voltages, but it also produces a record of these voltages, graphing them as a function of time. These graphs are displayed on a screen, much like the one found in a television. The vertical axis represents voltage, and the horizontal axis represents time, going from left to right. > electrode A conductive medium that can be used to apply electrical stimulation or to record electrical potentials. >> microelectrode A very fine electrode, generally used to record activity of individual neurons. [> membrane potential The electrical charge across a cell membrane; the difference in electrical potential inside and outside the cell. > escilloscope A laboratory instrument that is capable of displaying a graph of voltage as a function of time on the face of a cathode ray tube. 46 Chapter 2 Low Structure and Functions of Cells of the Nervous System High concentration — TD. concentration Naj Force of Electrostatic Force of Electrostatic Ouiaicio oie EH diffusion pressure diffusion Y pressure + + + + + + leave — Force of cell diffusion Inside of Cell y riGuRE 2.18 Control of the Membrane Potential Electrostatic Nat poe The figure shows the relative concentration of some important ions inside and outside the neuron and the forces acting on them. this ion within the cell contributes to the membrane po- tential, it is located where it is because the membrane is impermeable to it. The potassium ion K“ is concentrated within the axon; thus, the force of diffusion tends to push itout of the cell. However, the outside of the cell is charged positively with respect to the inside, so clectrostatic pressure tends to force this cation inside. Thus, the two opposing forces balance, and potassium ions tend to remain where they are. (Refer again to Figure 2.18.) The chloride ion CI” is in greatest concentration outside the axon. The force of diffusion pushes this ion inward. However, because the inside of the axon is neg- atively charged, electrostatic pressure pushes this anion outward. Again, two opposing forces balance each other. (Look again at Figure 2.18.) The sodium ion Na is also in greatest concentra- tion outside the axon, so it, like CI”, is pushed into the cell by the force of diffusion. But unlike chloride, the sodium ion is positively charged. Therefore, electrostatic pressure does not prevent Na” from entering the cell; indeed, the negative charge inside the axon attracts Na”. (Look once more at Figure 2.18.) How can Na” remain in greatest concentration in the extracellular fluid, despite the fact that both forces (diffusion and electrostatic pressure) tend to push it inside? The answer is this: Another force, provided by the sodium-potassium pump, continuously pushes Na* out of the axon. The sodium-potassium pump consists of a large number of protein molecules embedded in the membrane, driven by energy provided by molecules of ATP produced by the mitochondria. These mole- cules, known as sodium-potassium transporters, ex- change Na” for K*, pushing three sodium ions out for every two potassium ions they push in. (See Figure 2.19.) Because the membrane is not very permeable to Na”, sodium-potassium transporters very effectively keep the intracelular concentration of Na* low. By transporting K“ into the cell, they also increase the in- tracellular concentration of K' a small amount. The membrane is approximately 100 times more permeable to K* than to Na”, so the increase is slight; but, as we will see when we study the process of neural inhibition later in this chapter, it is very important. The transporters that make up the sodium-potassium pump use consid- erable energy: Up to 40 percent of a neuron's metabolic resources are used to operate them. Neurons, muscle cells, glia—in fact, most cells of the body—have sodium-— potassium transporters in their membrane. The Action Potential As we saw, the forces of both diffusion and electro- static pressure tend to push Na” into the cell. How- ever, the membrane is not very permeable to this ion, > sodium-potassium transporter A protein found in the membrane of all cells that extrudes sodium ions from and transports potassium ions into the cell. 3 sodium ions . pumped out Sodium-potassium transporter Membrane 9.9 Outside of Cell Inside of Cell (K$) 2 potassium ions pumped in riGuRE 2.19 A Sodium-Potassium Transporter These transporters are found in the cell membrane. and sodium-potassium transporters continuously pump out Na”, keeping the intracellular level of Na” low. But imagine what would happen if the membrane suddenly became permeable to Na”. The forces of dif fusion and electrostatic pressure would cause Na” to rush into the cell. This sudden influx (inflow) of posi- tively charged ions would drastically change the mem- brane potential. Indeed, experiments have shown that this mechanism is precisely what causes the action Protein subunits lons of ion channel Closed ion channel Lipid molecules in membrane Open ion channel FIGURE 2.20 lon Channels Communication Within a Neuron 47 potential: A brief increase in the permeability of the membrane to Na' (allowing these ions to rush into the cell) is immediately followed by a transient increase in the permeability of the membrane to K* (allowing these ions to rush out of the cell). What is responsible for these transient increases in permeability? We already saw that one type of protein molecule embedded in the membrane—the sodium-potassium transporter—actively pumps sodium ions out of the cell and pumps potassium ions into it. Another type of pro- tein molecule provides an opening that permits ions to enter or leave the cells. These molecules provide ion channels, which contain passages (“pores”) that can open or close. When an ion channel is open, a particular type ofion can flow through the pore and thus can enter or leave the cell. (See Figure 2.20.) Neural membranes contain many thousands of ion channels. For example, the giant squid axon contains several hundred sodium channels in each square micrometer of membrane. (There are one million square micrometers in a square millimeter; thus, a patch of axonal membrane the size of a lowercase letter o in this book would contain several hundred million sodium channels.) Each sodium chan- nel can admit up to 100 million ions per second when it is open. Thus, the permeability of a membrane to a particular ion at a given moment is determined by the number of ion channels that are open. The following numbered paragraphs describe the movements of ions through the membrane during the action potential. The numbers in the figure correspond > ion channel A specialized protein molecule that permits specific ions to enter or leave cells. Pore of ion channel Inside of Cell When ion channels are open, ions can pass through them, entering or leaving the cell. 48 Chapter 2 Structure and Functions of Cells of the Nervous System Sodium channel Refractory Reset E. Sodium ions enter +40 [Nat chameis 3 become refractory, no more Nat — enters cell z K+ continues to ob leave cell, E causes membrane s K+ channels potential to return 2 open, K+ to resting level o begins to leave 5 cell 5 5 Nat channels = open, Na+ begins to enter/ cell = E K+ channels close, / Na* channels reset -70 — Threshold of Extra K+ outside excitation diffuses away FIGURE 2.21 lon Movements During the Action Potential The shaded box at the top shows the opening of sodium channels at the threshold of excitation, their refractory condition at the peak of the action potential, and their resetting when the membrane potential returns to normal. to the numbers of the paragraphs that follow. (See Figure 2.21.) 1. As soon as the threshold of excitation is reached, the sodium channels in the membrane open, and Na rushes in, propelled by the forces of diffusion and electrostatic pressure. The opening of these channels is triggered by reduction of the mem- brane potential (depolarization); they open at the point at which an action potential begins: the threshold of excitation. Because these channels are opened by changes in the membrane potential, they are called voltage-dependent ion channels. The influx of positively charged sodium ions pro- duces a rapid change in the membrane potential, from —70 mV to +40 mV. 2. The membrane of the axon contains voltage-depen- dent potassium channels, but these channels are less sensitive than voltage-dependent sodium chan- nels. That is, they require a greater level of depolar- ization before they begin to open. Thus, they begin to open later than the sodium channels. o S*89 Action potential 5 E E E ê 5o Opening of Nat channels s 3 0 É o Opening of K+ channels 5 S o 5 & e 20 2 5 e z 5 =70 o e 5 8 õ Time ———» FIGURE 2.22. Permeability to lons During the Action Potential The graph shows changes in the permeability of the membrane of an axon to Na* and K* during the action potential. 3. At about the time the action potential reaches its peak (in approximately 1 msec), the sodium channels become refractor-—the channels become blocked and cannot open again until the mem- brane once more reaches the resting potential. At this time, no more Na* can enter the cell. 4. By now, the voltage-dependent potassium channels in the membrane are open, letting K” ions move freely through the membrane. At this time, the in- side of the axon is posilively charged, so K“ is driven out of the cell by diffusion and by electrostatic pres- sure. This outflow of cations causes the membrane potential to return toward its normal value. As it does so, the potassium channels begin to close again. 5. Once the membrane potential returns to normal, the sodium channels reset so that another depolar- ization can cause them to open again. 6. The membrane actually overshoots its resting value (70 mV) and only gradually returns to normal as the potassium channels finally close. Eventually, sodium- potassium transporters remove the Na” ions that leaked in and retrieve the K* ions that leaked out. Figure 2.29 illustrates the changes in permeability of the membrane to sodium and potassium ions during the action potential. (See Figure 2.22.) How much ionic flow is there? The increased per- meability of the membrane to Na” is brief, and diffu- sion over any appreciable distance takes some time. Thus, when I say, “Na” rushes in,” I do not mean that the axoplasm becomes flooded with Na”. At the peak of >> voltage-dependent ion channel An ion channel that opens or closes according to the value of the membrane potential. The message that is conducted down an axon is called an action potential. The membranes of all cells of the body are electrically charged, but only axons can produce action potentials. The resting membrane potential occurs because various ions are located in different concentrations in the fluid inside and outside the cell. The extracelular fluid (like seawater) is rich in Na* and CI”, and the intracellular fluid is rich in K* and various organic anions, designated as A”. The cell membrane is freely permeable to water, but its permeability to various ions—in particular, Na! and K'—is regulated by ion channels. When the membrane potential is at its resting value (-70 mV), the voltage-dependent sodium and potassium chan- nels are closed. Some Na* continuously leaks into the axon but is promptly forced out of the cell again by the sodium-potassium transporters (which also pump potassium into the axon). When an electrical stimula- tor depolarizes the membrane of the axon so that its potential reaches the threshold of excitation, voltage- dependent sodium channels open, and Na” rushes into the cell, driven by the force of diffusion and by electrostatic pressure. The entry of these positively charged ions further reduces the membrane potential and, indeed, causes it to reverse, so the inside becomes positive. The opening of the sodium chan- nels is temporary; they soon close again. The depo- larization caused by the influx of Na” activates voltage-dependent potassium channels, and K* leaves the axon, traveling down its concentration gradient. This efflux (outflow) of K* quickly brings the membrane potential back to its resting value. Communication Between Neurons Now that you know about the basic structure of neurons and the nature of the action potential, it is time to de- scribe the ways in which neurons can communicate with each other. These communications make it possible for circuits of neurons to gather sensory information, make plans, and initiate behaviors. The primary means of communication between neurons is synaptic transmission—the transmission of messages from one neuron to another through a syn- apse. As we saw, these messages are carried by neu- rotransmitters, released by terminal buttons. These Communication Between Neurons 51 Because an action potential of a given axon is an all-or-none phenomenon, neurons represent intensity by their rate of firing. The action potential normally begins at one end of the axon, where the axon attaches to the soma. The action potential travels continuously down unmyelinated axons, remaining constant in size, until it reaches the terminal buttons. (If the axon divides, an action potential continues down each branch.) In myelinated axons, ions can flow through the membrane only at the nodes of Ranvier, because the axons are covered everywhere else with myelin, which isolates them from the extra- cellular fluid. Thus, the action potential is conducted passively from one node of Ranvier to the next. When the electrical message reaches a node, voltage- dependent sodium channels open, and a new action potential is triggered. This mechanism saves a consid- erable amount of energy because sodium-potassium transporters are not needed along the myelinated portions of the axon, and saltatory conduction is faster. m THOUGHT QUESTION The evolution of the human brain, with all its com- plexity, depended on many apparently trivial mecha- nisms. For example, what if cells had not developed the ability to manufacture myelin? Unmyelinated axons must be very large if they are to transmit action potentials rapidly. How big would the human brain have to be if oligodendrocytes did not produce myelin? Could the human brain as we know it have evolved without myelin? chemicals diffuse across the fluid-filled gap between the terminal buttons and the membranes of the neurons with which they form synapses. As we will see in this sec- tion, neurotransmitters produce postsynaptic poten- tials—brief depolarizations or hyperpolarizations—that increase or decrease the rate of firing of the axon of the postsynaptic neuron. To see an interactive animation of the information presented in the following section, (> [ Simulate synapses on MyPsychLab. Neurotransmitters exert their effects on cells by at- taching to a particular region of a receptor molecule >> postsynaptic potential. Alterations in the membrane potential of a postsynaptic neuron, produced by liberation of neurotransmit- ter at the synapse. 52 Chapter 2 Structure and Functions of Cells of the Nervous System called the binding site. A molecule of the chemical fits into the binding site the way a key fits into a lock: The shape of the binding site and the shape of the molecule of the neurotransmitter are complementary. A chemical that attaches to a binding site is called a ligand, from ligare, “to bind.” Neurotransmitters are natural ligands, produced and released by neurons. But other chemicals found in nature (primarily in plants or in the poisonous venoms of animals) can serve as ligands too. In addition, artificial ligands can be produced in the laboratory. These chemicals are discussed in Chapter 4, which deals with drugs and their effects. Structure of Synapses As you have alrcady Icarncd, synapses are junctions be- twcen the terminal buttons at the ends of the axonal branches of one neuron and the membrane of another. Synapses can occur in three places: on dendrites, on the soma, and on other axons. These synapses are referred to as axodendritic, axosomatic, and axoaxonic. Axodendritic synapses can occur on the smooth surface of a dendrite or on dendritic spines—small protrusions that stud the dendrites of several types of large neurons in the brain. (Sce Figure 2.26.) Figure 2.27 illustrates a synapse. The presynaptic membrane, located at the end of the terminal button, faces the postsynaptic membrane, located on the neuron that receives the message (the postsynapticneuron). These two membranes face each other across the synaptic cleft, a gap that varies in size from synapse to synapse but is usually around 20 nm wide. (A nanometer, nm, is one Terminal button Dendritic spine h (a) (b) FIGURE 2.26 Types of Synapses billionth ofa meter.) The synaptic cleft contains extracel- lular fluid, through which the neurotransmitter diffuses. A meshwork of filaments crosses the synaptic cleft and keeps the presynaptic and postsynaptic membranes in alignment. (Sec Figure 2.27.) As you may have noticed in Figure 2.27, two promi- nent structures are located in the cytoplasm of the ter- minal button: mitochondria and synaptic vesicles. We also see microtubules, which are responsible for trans- porting material between the soma and terminal but- ton. The presence of mitochondria implies that the ter- minal button needs energy to perform its functions. Synaptic vesicles are small, rounded objects in the shape of spheres or ovoids. (The term vesicle means “little bladder.”) A given terminal button can contain from a few hundred to nearly a million synaptic vesicles. Many terminal buttons contain two types of synaptic vesicles: > g site The location on a receptor protein to which a ligand binds. > ligand (lye gand or ligg and) A chemical that binds with the binding site of a receptor. [> dendritic spine A small bud on the surface of a dendrite, with which a terminal button of another neuron forms a synapse. [> presynaptic membrane The membrane of a terminal button that lies adjacent to the postsynaptic membrane and through which the neurotransmitter is released. > postsynaptic membrane The cell membrane opposite the terminal button in a synapse; the membrane of the cell that receives the message. [> synaptic cleft The space between the presynaptic membrane and the postsynaptic membrane. Presynaptic Somatic terminal button membrane Pestana Terminal terminal button — button (c) (a) Axodendritic synapses can occur on the smooth surface of a dendrite (a) or on dendritic spines (b). Axosomatic synapses occur on somatic membrane (c). Axoaxonic synapses consist of synapses between two terminal buttons (d).  Neuron FIGURE 2.27 Details of a Synapse large and small. Small synaptic vesicles (found in all terminal buttons) contain molecules of the neurotrans- mitter. They range in number from a few dozen to sev- eral hundred. The membrane of small synaptic vesicles consists of approximately 10,000 lipid molecules into which are inserted about 200 protein molecules. Trans- port proteins fill vesicles with the neurotransmitter, and trafficking proteins are involved in the release of neu- rotransmitter and recycling of the vesicles. Synaptic ves- icles are found in greatest numbers around the part of the presynaptic membrane that faces the synaptic cleft— near the release zone, the region from which the neu- rotransmitter is released. In many terminal buttons we see a scattering of large, dense-core synaptic vesicles. These vesicles contain one of a number of different peptides, the functions of which are described later in this chapter. (See Figures 2.27 and 2.28.) Small synaptic vesicles are produced in the Golgi apparatus located in the soma and are carried by fast axoplasmic transport to the terminal button. As we will see, some are also produced from recycled material in the terminal button. Large synaptic vesicles are pro- duced only in the soma and are transported through the axoplasm to the terminal buttons. In an electron micrograph the postsynaptic mem- brane under the terminal button appears somewhat thicker and more dense than the membrane elsewherce. This postsynaptic density is caused by the presence of receptors—specialized protein molecules that detect the presence of neurotransmitters in the synaptic cleft— and protein filaments that hold the receptors in place. (Look again at Figures 2.27 and 2.28.) Communication Between Neurons 53 Detail of Synapse Mitochondrion Microtubule Synaptic vesicle being transported from soma Terminal button FIGURE 2.28 Cross Section of a Synapse The photograph from an electron microscope shows a cross section of a synapse. The terminal button contains many synaptic vesicles, filled with the neurotransmitter, and a single large dense-core vesicle, filled with a peptide. (From De Camilli et al., in Synapses, edited by W. M. Cowan, T. C. Súdhof, and C. F. Stevens. Baltimore, MD: Johns Hopkins University Press, 2001. Reprinted with permission) > synaptic vesicle (vess | kul) A small, hollow, beadlike structure found in terminal buttons; contains molecules of a neurotransmitter. > release zone A region of the interior of the presynaptic membrane of a synapse to which synaptic vesicles attach and release their neurotransmitter into the synaptic cleft. 56 Chapter 2 Structure and Functions of Cells of the Nervous System : Bulk rendocytosis Merge and recycle FIGURE 2.32 Recycling of the Membrane of Synaptic Vesicles After synaptic vesicles have released neurotransmitter into the synaptic cleft, the following takes place: In "kiss and run," the vesicle fuses with the presynaptic membrane, releases the neurotransmitter, reseals, leaves the docking site, becomes refilled with the neurotransmitter, and mixes with other vesicles in the terminal button. In "merge and recycle," the vesicle completely fuses with the postsynaptic membrane, losing its identity. Extra membrane from fused vesicles pinches off into the cytoplasm and forms vesicles, which are filled with the neurotransmitter. The membranes of vesicles in the reserve pool are recycled through a process of bulk endocytosis. Large pieces of the membrane of the terminal button fold inward, break off, and enter the cytoplasm. New vesicles are formed from small buds that break off of these pieces of membrane. Activation of Receptors How do molecules of the neurotransmitter produce a depolarization or hyperpolarization in the postsynaptic membrane? They do so by diffusing across the synaptic cleft and attaching to the binding sites of special protein molecules located in the postsynaptic membrane, called postsynaptic receptors. Once binding occurs, the postsyn- aptic receptors open neurotransmitter-dependent ion channels, which permit the passage of specific ions into or outofthe cell. Thus, the presence of the neurotransmitter in the synaptic cleft allows particular ions to pass through the membrane, changing the local membrane potential. Neurotransmitters open ion channels by at least two different methods, direct and indirect. The direct o Molecule of neurotransmitter attached to binding site Binding site of receptor Opei ion channel ion channel o [] FIGURE 2.33 lonotropic Receptors The ion channel opens when a molecule of neurotransmitter attaches to the binding site. For purposes of clarity the drawing is schematic; molecules of neurotransmitter are actually much larger than individual ions. method is simpler, so 1 will describe it first. Figure 2.33 illustrates a neurotransmitter-dependent ion channel that is equipped with its own binding site. When a mole- cule of the appropriate neurotransmitter attaches to it, the ion channel opens. The formal name for this com- bination receptor/ion channel is an ionotropic recep- tor. (Sce Figure 2.33.) Tonotropic receptors were first discovered in the or- gan that produces electrical current in Torpedo, the clec- tric ray, where they occur in great number. (The electric ray is a fish that gencrates a powerful electrical current, not some kind of Star Wars weapon.) These receptors, which are sensitive to a neurotransmitter called acetylcho- line, contain sodium channels. When these channels are open, sodium ions enter the cell and depolarize the membrane. [> postsynaptic receptor A receptor molecule in the postsynap- tic membrane of a synapse that contains a binding site for a neurotransmitter. [> neurotransmitter-dependent ion channel An ion channel that opens when a molecule of a neurotransmitter binds with a postsynaptic receptor. > ionotropic receptor (eye on oh trow pik) A receptor that contains a binding site for a neurotransmitter and an ion channel that opens when a molecule of the neurotransmitter attaches to the binding site. The indirect method is more complicated. Some receptors do not open ion channels directly but instead start a chain of chemical events. These receptors are called metabotropic receptors because they involve steps that require that the cell expend metabolic en- ergy. Metabotropic receptors are located in close prox- imity to another protein attached to the membrane—a G protein. When a molecule of the neurotransmitter binds with the receptor, the receptor activates a G pro- tein situated inside the membrane next to the receptor. When activated, the G protein activates an enzyme that stimulates the production of a chemical called a second messenger. (The neurotransmitter is the first messen- ger.) Molecules of the second messenger travel through the cytoplasm, attach themselves to nearby ion chan- nels, and cause them to open. Comparcd with postsyn- aptic potentials produced by ionotropic receptors, those produced by metabotropic receptors take longer to begin and last longer. (See Figure 2.34.) The first second messenger to be discovered was oy- clic AMP, a chemical that is synthesized from ATP. Since then, several other second messengers have been discov- ered. As you will see in later chapters, second messengers play an important role in both synaptic and nonsynaptic communication. And they can do more than open ion channels. For example, they can travel to the nucleus or other regions of the neuron and initiate biochemical changes that affect the functions of the cell. They can Surface of membrane Molecule of neurotransmitter Metabotropic receptor Open ion channel Molecule of neurotransmitter Closed ion attached to binding site of channel metabotropic receptor FIGURE 2.34 Metabotropic Receptors When a molecule of neurotransmitter binds with a receptor, a G protein activates an enzyme, which produces a second messenger (represented by black arrows) that opens nearby ion channels. Communication Between Neurons 57 even tum specific genes on or off, thus initiating or ter- minating production of particular proteins. Postsynaptic Potentials As I mentioned earlier, postsynaptic potentials can be either depolarizing (excitatory) or hyperpolarizing (inhibitory). What determines the nature of the post- synaptic potential at a particular synapse is not the neurotransmitter itself. Instead, it is determined by the characteristics of the postsynaptic receptors—in parti- cular, by the particular type of ion channel they open. As Figure 2.35 shows, four major types of neurotrans- mitter-dependent ion channels are found in the postsyn- aptic membrane: sodium (Na'), potassium (K”), chloride (CI), and calcium (Ca?*). Although the figure depicis only directly activated (ionotropic) ion channels, you should realize that many ion channels are activated indi- rectly, by metabotropic receptors coupled to G proteins. The neurotransmitter-dependent sodium channel is the most important source of excitatory postsynaptic po- tentials. As we saw, sodium-potassium transporters keep sodium outside the cell, waiting for the forces of diffusion and electrostatic pressure to push it in. Obviously, when sodium channels are opened, the result is a depolariza- tion—an excitatory postsynaptic potential (EPSP). (See Figure 2.35a.) We also saw that sodium-potassium trans- porters maintain a small surplus of potassium ions inside the cell. If potassium channels open, some of these cations will follow this gradient and leave the cell. Because K* is positively charged, its efflux will hyperpolarize the mem- brane, producing an inhibitory postsynaptic potential (IPSP). (See Figure 2.35b.) At many synapses, inhibitory neurotransmitters open the chloride channels, instead of (orin addition to) potassium channels. The effect ofopen- ing chloride channels depends on the membrane potential of the neuron. If the membrane is at the resting potential, >> metabotropic receptor (meh tab oh trow pik) A receptor that contains a binding site for a neurotransmitter; activates an enzyme that begins a series of events that opens an ion channel elsewhere in the membrane of the cell when a molecule of the neurotransmitter attaches to the binding site. &> 6 protein A protein coupled to a metabotropic receptor; conveys messages to other molecules when a ligand binds with and activates the receptor. [> second messenger A chemical produced when a G protein activates an enzyme; carries a signal that results in the opening of the ion channel or causes other events to occur in the cell. > excitatory postsynaptic potential (EPSP) An excitatory depolarization of the postsynaptic membrane of a synapse caused by the liberation of a neurotransmitter by the terminal button. >> inhibitory postsynaptic potential (IPSP) An inhibitory hyperpolarization of the postsynaptic membrane of a synapse caused by the liberation of a neurotransmitter by the terminal button. 58 Chapter 2 Structure and Functions of Cells of the Nervous System Molecule of neurotransmitter attached to binding site lon channel Influx of Na* causes depolarization (EPSP) Efflux of K* causes hyperpolarization (IPSP) Membrane Outside of Cell Influx of CI causes hyperpolarization (IPSP) Influx of Ca?+ activates enzyme FIGURE 2.35 lonic Movements During Postsynaptic Potentials nothing happens, because (as we saw carlicr) the forces of diffusion and electrostatic pressure balance perfectly for the chloride ion. However, if the membrane potential has already been depolarized by the activity of excitatory syn- apses located nearby, then the opening of chloride chan- nels will permit CI” to enter the cell. The influx of anions will bring the membrane potential back to its normal rest- ing condition. Thus, the opening of chloride channels serves to neutralize EPSPs. (See Figure 2.35c.) The fourth type of neurotransmitter-dependent ion channel is the calcium channel. Calcium ions (Ca?'), being positively charged and being located in highest concentration outside the cell, act like sodium ions; that is, the opening of calcium channels depolarizes the membrane, producing EPSPs. But calcium does even more. As we saw earlier in this chapter, the entry of cal- cium into the terminal button triggers the migration of synaptic vesicles and the release of the neurotransmitter. In the dendrites of the postsynaptic cell, calcium binds with and activates special enzymes. These enzymes have a variety of effects, including the production of biochem- ical and structural changes in the postsynaptic neuron. As we will see in Chapter 13, one of the ways in which learning affects the connections between neurons in- volves changes in dendritic spines initiated by the open- ing of calcium channels. (See Figure 2.35d.) Termination of Postsynaptic Potentials Postsynaptic potentials are brief depolarizations or hyper- polarizations caused by the activation of postsynaptic receptors with molecules of a neurotransmitter. They are kept brief by two mechanisms: reuptake and enzy- matic deactivation. The postsynaptic potentials produced by most neurotransmitters are terminated by reuptake. This process is simply an extremely rapid removal of neu- rotransmitter from the synaptic cleft by the terminal button. The neurotransmitter does not return in the vesicles that get pinched off the membrane of the terminal button. Instead, the membrane contains special transporter molecules that draw on the cells energy reserves to force molecules of the neurotrans- mitter from the synaptic cleft directly into the cyto- plasm—just as sodium-potassium transporters move Na* and Kº across the membrane. When an action potential arrives, the terminal button releases a small amount of neurotransmitter into the synaptic cleft and then takes it back, giving the postsynaptic recep- tors only a brief exposure to the neurotransmitter. (See Figure 2.36.) Enzymatic deactivation is accomplished by an en- zyme that destroys molecules of the neurotransmit- ter. Postsynaptic potentials are terminated in this way for acetylcholine (ACh) and for neurotransmitters that consist of peptide molecules. Transmission at [> reuptake The reentry of a neurotransmitter just liberated by a terminal button back through its membrane, thus terminating the postsynaptic potential. [> enzymatic deactivation The destruction of a neurotransmitter by an enzyme after its release—for example, the destruction of acetylcholine by acetylcholinesterase. Activity of excitatory synapses produces EPSPs (red) in postsynaptic neuron Axon hillock reaches threshold of excitation; action potential is triggered in axon (a) rIGURE 2.37 Neural Integration Communication Between Neurons 61 Activity of inhibitory Ssynapses produces IPSPs (blue) in postsynaptic neuron IPSPs counteract EPSP: action potential is not triggered in axon (b) (a) If several excitatory synapses are active at the same time, the EPSPs they produce (shown in red) summate as they travel toward the axon, and the axon fires. (b) If several inhibitory synapses are active at the same time, the IPSPs they produce (shown in blue) diminish the size of the EPSPs and prevent the axon from firing. the neuron causes a decrease in the rate of synthesis or release of the neurotransmitter. Most investigators be- lieve that autoreceptors are part of a regulatory system that controls the amount of neurotransmitter that is re- leased. If too much is released, the autoreceptors inhibit both production and release; if not enough is released, the rates of production and release go up. Other Types of Synapses So far, the discussion of synaptic activity has referred only to the effects of postsynaptic excitation or inhibi- tion. These effects occur at axosomatic or axodendritic synapses. Axoaxonic synapses work differently. Axoax- onic synapses do not contribute directly to neural inte- gration. Instead, they alter the amount of neurotrans- mitter released by the terminal buttons of the postsynaptic axon. They can produce presynaptic modu- lation: presynaptic inhibition or presynaptic facilitation. As you know, the release of a neurotransmitter by a terminal button is initiated by an action potential. Nor- mally, a particular terminal button releases a fixed amount of neurotransmitter each time an action poten- tial arrives. However, the release of neurotransmitter can be modulated by the activity of axoaxonic synapses. If the activity of the axoaxonic synapse decreases the release of the neurotransmitter, the effect is called presynaptic inhibition. If it increases the release, it is called presynaptic facilitation. (See Figure 2.38.) By the way, as we will see in Chapter 4, the active ingredient in marijuana exerts its effects on the brain by binding with presynaptic receptors. Many very small neurons have extremely short pro- cesses and apparently lack axons. These neurons form dendrodendritic synapses, or synapses between dendrites. Because these neurons lack long axonal processes, they do not transmit information from place to place within the brain. Most investigators believe that they perform regulatory functions, perhaps helping to organize the activity of groups ofneurons. Because these neurons are so small, they are difficult to study; therefore, little is known about their function. >> presynaptic inhibition The action of a presynaptic terminal button in an axoaxonic synapse; reduces the amount of neu- rotransmitter released by the postsynaptic terminal button. >> presynaptic facilitation The action of a presynaptic terminal button in an axoaxonic synapse; increases the amount of neu- rotransmitter released by the postsynaptic terminal button. 62 Chapter 2 Structure and Functions of Cells of the Nervous System Terminal button A Axoaxonic Terminal synapse button B Postsynaptic. density Dendritic spine FIGURE 2.38 An Axoaxonic Synapse The activity of terminal button A can increase or decrease the amount of neurotransmitter released by terminal button B. Some larger neurons, as well, form dendroden- dritic synapses. Some of these synapses arc chemical, indicated by the presence of synaptic vesicles in one of the juxtaposed dendrites and a postsynaptic thicken- ing in the membrane of the other. Other synapses are electrical; the membranes meet and almost touch, form- ing a gap junction. The membranes on both sides of a gap junction contain channels that permit ions to dif- fuse from one cell to another. Thus, changes in the membrane potential of one neuron induce changes in the membrane of the other. (See Figure 2.39.) AI- though most gap junctions in vertebrate synapses are dendrodendritic, axosomatic and axodendritic gap junctions also occur. Gap junctions are common in invertebrates; their function in the vertebrate nervous system is not known. Nonsynaptic Chemical Communication Neurotransmitters are released by terminal buttons of neurons and bind with receptors in the membrane of another cell located a very short distance away. The com- munication at cach synapsc is private. Neuromodulators are chemicals released by neurons that travel farther and FIGURE 2.39 A Gap Junction A gap junction permits direct electrical coupling between the membranes of adjacent neurons. (From Bennett, M. V. L., and Pappas, G. D. The Journal of Neuroscience, 1983, 3, 748-761. Reprinted with permission.) are dispersed more widely than are neurotransmitters. Most neuromodulators are peptides, chains of amino acids that are linked together by chemical attachments called peptide bonds (hence their name). Neuromodula- tors are secreted in larger amounts and diffuse for lon- ger distances, modulating the activity of many neurons in a particular part of the brain. For example, neuro- modulators affect general behavioral states such as vigi- lance, fearfulness, and sensitivity to pain. Chapter 4 dis- cusses the most important neurotransmitters and neuromodulators. Hormones are secreted by cells of endocrine glands (from the Greek endo-, “within,” and krinein, “to secrete”) or by cells located in various organs, such as the stomach, the intestines, the kidneys, and the brain. Cells that secrete hormones release these chemicals >> gap junction A special junction between cells that per direct communication by means of electrical coupling. [> neuromodulator A naturally secreted substance that acts like a neurotransmitter except that it is not restricted to the synaptic cleft but diffuses through the extracelular fluid. [> peptide A chain of amino acids joined together by peptide bonds. Most neuromodulators, and some hormones, consist of peptide molecules. [> hormone A chemical substance that is released by an endocrine gland that has effects on target cells in other organs. [> endocrine gland A gland that liberates its secretions into the extracelular fluid around capillaries and hence into the bloodstream.  Detail of Cell Molecule of steroid hormone Vo FIGURE 2.40 Action of Steroid Hormones Steroid hormones affect their target cells by means of specialized receptors in the nucleus. Once a receptor binds with a molecule of a steroid hormone, it causes genetic mechanisms to initiate protein synthesis. SECTION SUMMARY Communication Between Neurons 63 into the extracelular fluid. The hormones are then distributed to the rest of the body through the blood- stream. Hormones affect the activity of cells (includ- ing neurons) that contain specialized receptors lo- cated either on the surface of their membrane or deep within their nuclei. Cells that contain receptors for a particular hormone are referred to as target cells for that hormone; only these cells respond to its presence. Many neurons contain hormone receptors, and hor- mones are able to affect behavior by stimulating the receptors and changing the activity of these neurons. For example, a sex hormone, testosterone, increases the aggressiveness of most male mammails. Peptide hormones exert their effects on target cells by stimulating metabotropic receptors located in the membrane. The second messenger that is generated travels to the nucleus of the cell, where it initiates changes in the cell's physiological processes. Steroid hormones consist of very small fat-soluble molecules. (Steroid derives from the Greek stereos, “solid,” and Latin oleum, “oil.” They are synthesized from cholesterol.) Ex- amples of steroid hormones include the sex hormones secreted by the ovaries and testes and the hormones secreted by the adrenal cortex. Because steroid hor- mones are soluble in lipids, they pass easily through the cell membrane. They travel to the nucleus, where they attach themselves to receptors located there. The re- ceptors, stimulated by the hormone, then direct the machinery of the cell to alter its protein production. (See Figure 2.40.) In the past few years, investigators have discovered the presence of steroid receptors in terminal buttons and around the postsynaptic membrane of some neu- rons. These steroid receptors influence synaptic trans- mission, and they do so rapidly. Exactly how they work is still not known. > target cell The type of cell that is directly affected by a hormone or other chemical signal. > steroid A chemical of low molecular weight, derived from cholesterol. Steroid hormones affect their target cells by attaching to receptors found within the nucleus. Synapses consist of junctions between the terminal buttons of one neuron and the membrane, another neuron, a muscle cell, or a gland cell. When an action potential is transmitted down an axon, the terminal Communication Between Neurons buttons at the end release a neurotransmitter, a chemical that produces either depolarizations (EPSPs) or hyperpolarizations (IPSPs) of the postsynaptic (continued on next page)  Structure of the Nervous System An Overview Meninges The Ventricular System and Production of CSF Section Summary Development of the Central Nervous System The Forebrain The Midbrain The Hindbrain The Spinal Cord Section Summary Spinal Nerves Cranial Nerves The Autonomic Nervous System Section Summary Ryan B., a college freshman, had suffered from occa- sional epileptic seizures since childhood. He had been taking drugs for his seizures for many years, but lately the medication wasn't helping—his seizures were becoming more frequent. His neurologist increased the dose of the medication, but the seizures persisted, and the drug made it difficult for Ryan to concentrate on his studies. He was afraid that he would have to drop out of school. He made an appointment with his neurologist and asked whether another drug was available that might work better and not affect his ability to concentrate. “No,” said the neurologist, "you're taking the best medication we have right now. But | want to send you to Dr. L., a neuro- surgeon at the medical school. | think you might be a good candidate for seizure surgery.” Ryan had a focal-seizure disorder. His problems were caused by a localized region of the brain that contained some scar tissue. Periodically, this region would irritate the surrounding areas, triggering epileptic seizures—wild, sustained firing of cerebral neurons that result in cognitive disruption and, sometimes, uncontrolled movements. Ryan's focus was probably a result of brain damage that occurred when he was born. Dr. L. ordered some tests that indicated that the seizure focus was located in the left side of his brain, in a region known as the medial temporal lobe. Ryan was surprised to learn that he would remain awake during his surgery. In fact, he would be called on to provide information that the surgeon would need to remove a region of his brain that included the seizure focus. As you might expect, he was nervous when he was wheeled into the surgery, but after the anesthesiolo- gist injected something through the tube in one of his he goal of neuroscience research is to under- stand how the brain works. To understand the results of this research, you must be ac- quainted with the basic structure of the nervous sys- tem. The number of terms introduced in this chap- ter is kept to a minimum (but as you will see, the minimum is still a rather large number). With the framework you will receive from this chapter and from the features on (>| MyPsychtab, you should have no trouble learning the material presented in subsequent chapters. Basic Features of the Nervous System 67 veins, Ryan relaxed and thought to himself, “This won't be too bad.” Dr. L. marked something on his scalp, which had previously been shaved, and then made several injections of a local anesthetic. Then he cut the scalp and injected some more anesthetic. Finally, he used a dfrill and a saw to remove a piece of skull. He then cut and folded back the thick membrane that covers the brain, exposing the surface of the brain. When removing a seizure focus, the surgeon wants to cut away all the abnormal tissue while sparing brain tissue that performs important functions, such as the comprehension and production of speech. For this reason, Dr. L. began stimulating parts of the brain to determine which regions he could safely remove. To do so, he placed a metal probe against the surface of Ryan's brain and pressed a pedal that delivered a weak electri- cal current. The stimulation disrupts the firing patterns of the neurons located near the probe, preventing them from carrying out their normal functions. Dr. L. found that stimulation of parts of the temporal lobe disrupted Ryan's ability to understand what he and his associates were saying. When he removed the part of the brain contain- ing the seizure focus, he was careful not to damage these regions. The operation was successful. Ryan continued to take his medication but at a much lower dose. His seizures disappeared, and he found it easier to concentrate in class. I met Ryan during his junior year, when he took a course I was teaching. | described seizure surgery to the class one day, and after the lecture he approached me and told me about his experience. He received the third highest grade in the class. Basic Features of the Nervous System Before beginning a description of the nervous system, I want to discuss the terms that are used to describe it. The gross anatomy of the brain was described long ago, and everything that could be seen without the aid of a microscope was given a name. Early anatomists named most brain structures according to their similarity to commonplace objects: amygdala, or “almond-shaped 68 Chapter 3 Structure of the Nervous System object”; hippocampus, or “sea horse”; genu, or “knee”; cortex, or “bark”; pons, or “bridge”; uncus, or “hook,” to give a few examples. Throughout this book 1 will translate the names of anatomical terms as I introduce them, because the translation makes the terms more memorable. For example, knowing that cortes means “bark” (like the bark of a tree) will help you to remem- ber that the cortex is the outer layer of the brain. When describing features of a structure as complex as the brain, we need to use terms denoting directions. Directions in the nervous system are normally described relative to the neuraxis, an imaginary line drawn through the length of the central nervous system, from the lower end of the spinal cord up to the front of the brain. For simplicity's sake, let us consider an animal with a straight ncuraxis. Figure 3.1 shows an alligator and two humans. This alligator is certainly laid outin a linear fashion; we can draw a straight line that starts between its eyes and continues down the center of its spinal cord. (See Figure 3.1.) The front end is anterior, and the tail is posterior. The terms rostral (toward the beak) and caudal (toward the tail) are also employed, especially when referring specifically to the brain. The top of the head and the back are part of the dorsal sur- Dorsal Rostral or anterior Neuraxis Ventral Dorsal Rostral or anterior ” 4 Neuraxis Ventral Caudal or posterior FIGURE 3.1 Views of Alligator and Human face, while the ventral (front) surface faces the ground. (Dorsum means “back” and ventrum means “belly.”) These directions are somewhat more complicated in the human; because we stand upright, our neuraxis bends, so the top of the head is perpendicular to the > neuraxis An imaginary line drawn through the center of the length of the central nervous system, from the bottom of the spinal cord to the front of the forebrain. > anterior With respect to the central nervous system, located near or toward the head. > posterior With respect to the central nervous system, located near or toward the tail. [> rostral “Toward the beak”; with respect to the central nervous system, in a direction along the neuraxis toward the front of the face. > caudal “Toward the tail”; with respect to the central nervous system, in a direction along the neuraxis away from the front of the face, [> dorsal “Toward the back”; with respect to the central nervous system, in a direction perpendicular to the neuraxis toward the top ofthe head or the back. > ventral “Toward the belly”; with respect to the central nervous system, in a direction perpendicular to the neuraxis toward the bottom of the skull or the front surface of the body. Dorsal Lateral «—— —p Lateral Medial —»; -«— Medial Caudal or osterior Ventral Dorsal —p Lateral <— Medial Lateral «— Medial —» | 88 Caudal or posterior These side and frontal views show the terms used to denote anatomical directions.  Meninges Opening cut in meninges 7 to show brain Central Nervous System: Brain Cauda equina Edge of dura mater (cut open) Spinal nerves (a) FIGURE 3.3 The Nervous System Layers of meninges Basic Features of the Nervous System n Dura mater Arachnoid membrane Subarachnoid space (filled with cerebrospinal fluid) Arachnoid trabeculae Pia mater Surface of brain Spinal cord Pia mater (adheres to spinal cord) a Spinal nerve Arachnoid membrane Dura mater Vertebra The figures show (a) the relation of the nervous system to the rest of the body, (b) detail of the meninges that cover the central nervous system, and (c) a closer view of the lower spinal cord and cauda equina. The Ventricular System and Production of CSF The brain is very soft and jellylike. The considerable weight ofa human brain (approximately 1400 g), along with its delicate construction, necessitates that it be protected from shock. A human brain cannot even sup- port its own weight well; it is difficult to remove and handle a fresh brain from a recently deceased human without damaging it. Fortunately, the intact brain within a living human is well protected. It floats in a bath of CSF contained 72 Chapter 3 Structure ofthe Nervous System ventricle Massa intermedia Cerebral aqueduct (a) Choroid plexus of lateral ventricle Fourth ventricle ventricle aqueduct Arachnoid granulation Superior sagittal sinus Choroid plexus of third ventricle Cerebral aqueduct Subarachnoid space Subarachnoid pac Third ventricle space Cerebral aqueduct Choroid plexus Opening into FIGURE 3.4 The Ventricular System of the Brain of fourth ventricle subarachnoid space (a) The figure shows (a) a lateral view of the left side of the brain, (b) a frontal view, (c) a dorsal view, and (d) the production, circulation, and reabsorption of cerebrospinal fluid. within the subarachnoid space. Because the brain is completely immersed in liquid, its net weight is reduced to approximately 80 g; thus, pressure on the base of the brain is considerably diminished. The CSF surrounding the brain and spinal cord also reduces the shock to the central nervous system that would be caused by sudden head movement. The brain contains a series of hollow, intercon- nected chambers called ventricles (“little bellies”), which are filled with CSF. (See Figure 3.4.) The largest chambers are the lateral ventricles, which are con- nected to the third ventricle. The third ventricle is located at the midline of the brain; its walls divide the > ventricle (ven trik ul) One of the hollow spaces within the brain, filled with cerebrospinal fluid. >> lateral ventricle One of the two ventricles located in the center of the telencephalon. [third ventricle The ventricle located in the center of the diencephalon.  FIGURE 3.5 A Scanning Electron Micrograph of the Choroid Plexus BV = blood vessel, CE = choroid plexus, V = ventricle. (From Tissues and Organs: A Text-Atlas of Scanning Electron Microscopy, by Richard G. Kessel and Randy H. Kardon. Copyright O 1979 by W. H. Freem: Co. Reprinted by permission of Barbara Kessel and Randy Kardon.) and surrounding part of the brain into symmetrical halves. A bridge of neural tissue called the massa intermedia crosses through the middle of the third ventricle and serves as a convenient reference point. The cerebral aqueduct, a long tube, connects the third ventricle to the fourth ventricle. The lateral ventricles constitute the first and second ventricles, but they are never referred to as such. (Look again at Figure 3.4.) Cerebrospinal fluid is extracted from the blood and resembles blood plasma in its composition. CSF is man- ufactured by special tissue with an especially rich blood supply called the choroid plexus, which protrudes into all four of the ventricles. CSF is produced continuously; the total volume of CSF is approximately 125 ml, and the halflife (the time it takes for half of the CSF present in the ventricular system to be replaced by fresh fluid) is about 3 hours. Therefore, several times this amount is produced by the choroid plexus each day. The continu- ous production of CSF means that there must be a mechanism for its removal. The production, circulation, and reabsorption of CSF are illustrated in Figure 3.4d. A scanning electron micrograph of the choroid plexus is shown in Figure 3.5. Figure 3.4(d) shows a slightly rotated midsagittal view of the central nervous system, which shows only the right lateral ventricle (because the left hemi- sphere has been removed). Cerebrospinal fluid is pro- duced by the choroid plexus of the lateral ventricles, and it flows into the third ventricle. More CSF is pro- duced in this ventricle, which then flows through the Basic Features of the Nervous System 73 cerebral aqueduct to the fourth ventricle, where still more CSF is produced. The CSF leaves the fourth ventricle through small openings that connect with the subarachnoid space surrounding the brain. The CSF then flows through the subarachnoid space around the central nervous system, where it is reab- sorbed into the blood supply through the arachnoid granulations. These pouch-shaped structures pro- trude into the superior sagittal sinus, a blood vessel that drains into the veins serving the brain. (Look again at Figure 3.4d and (9) Simulate meninges and CsF on MyPsychLab.) Occasionally, the flow of CSF is interrupted at some point in its route of passage. For example, a brain tumor growing in the midbrain may push against the cerebral aqueduct, blocking its flow, or an infant may be born with a cerebral aqueduct that is too small to accommodate a normal flow of CSF. This occlusion results in greatly increased pressure within the ventricles, because the choroid plexus continues to produce CSF. The walls of the ventricles then ex- pand and produce a condition known as obstructive hydrocephalus (Aydrocephalus literally means “water- head”). If the obstruction remains and if nothing is done to reverse the increased intracerebral pressure, blood vessels will be occluded, and permanent—per- haps fatal—brain damage will occur. Fortunately, a surgeon can usually operate on the person, drilling a hole through the skull and inserting a shunt tube into one of the ventricles. The tube is then placed beneath the skin and connected to a pressure relief valve that is implanted in the abdominal cavity. When the pres- sure in the ventricles becomes excessive, the valve permits the CSF to escape into the abdomen, where it is eventually reabsorbed into the blood supply. (See Figure 3.6.) > cerebral aqueduct A narrow tube interconnecting the third and fourth ventricles of the brain, located in the center of the mesencephalon. > fourth ventricle The ventricle located between the cerebellum and the dorsal pons, in the center of the metencephalon. > choroid plexus The highly vascular tissue that protrudes into the ventricles and produces cerebrospinal fluid. >> arachnoid granulation Small projections of the arachnoid membrane through the dura mater into the superior sagittal sinus; CSF flows through them to be reabsorbed into the blood supply. > superior sagittal sinus A venous sinus located in the midline just dorsal to the corpus callosum, between the two cerebral hemispheres. > obstructive hydrocephalus A condition in which all or some of the brain's ventricles are enlarged; caused by an obstruction that impedes the normal flow of CSF. 76 Forebrain Midbrain Hindbrain Rostral Caudal (a) Dorsal C PP a Ventral (o) Chapter 3 Structure of the Nervous System Telencephalon Mesencephalon Cerebral hemisphere Metencephalon Thalamus Myelencephalon Diencéphalon Hypothalamus , o) Pituitary e gland Cerebral Basal Thalamus NMiabrain cortex ganglia Brain NPons pm Stem N medula Corebellum Corebellum Spinal cord (e) Medulla | q Spinal Hypothalimus Tegmentum Pons cord (a) FIGURE 3.8 Brain Development This schematic outline of brain development shows its relation to the ventricles. Views (a) and (9) show early development. Views (b) and (d) show later development. View (e) shows a lateral view of the left side of a semitransparent human brain with the brain stem “ghosted in.” The colors of all figures denote corresponding regions. The stem cells that give rise to the cells of the brain are known as progenitor cells. (A progenitor is a direct ancestor of a line of descendants.) During the first phase of development, progenitor cells in the ventricular zone (VZ), located just outside the wall of the neural tube, divide, making new progenitor cells and increasing the size of the ventricular zone. Some progenitor cells migrate a short distance away from the ventricular zone, where they continue to divide into more progenitor cells and establish the subventricular zone (SVZ). This phase is referred to as symmetrical division, because the divi- sion of cach progenitor cell produces two new progenitor TABLE 3.2 Anatomical Subdivisions of the Brain Major division Ventricle Subdivision Principal structures Myelencephalon Medulla oblongata cells. This form of division increases the size of the ven- tricular and subventricular zones. Then, seven weeks after conception, progenitor cells receive a signal to begin a period of asymmetrical division. During this phase, progenitor cells form two different kinds of cells as they divide: another progenitor cell and a brain cell. The first brain cells produced through asymmetri- cal division are radial glia. The cell bodies of radial glia remain close to the wall of the neural tube, in the VZ and SVZ, but they extend fibers radially outward from the ventricular zone, like spokes in a wheel. These fi- bers end in cuplike feet that attach to the pia mater, located at the outer surface of what becomes the cere- bral cortex. As the cortex becomes thicker, the fibers of the radial glia grow longer and maintain their connec- tions with the pia mater. (See Figure 3.9.) The period of asymmetrical division lasts about three months. Because the human cerebral cortex con- tains about 100 billion neurons, there are about one billion neurons migrating along radial glial fibers on a The Central Nervous System 77 given day. The migration path of the earliest neurons is the shortest and takes about one day. The neurons that produce the last, outermost layer have to pass through > progenitor cells Cells of the ventricular zone that divide and give rise to cells of the central nervous system. > ventricular zone (VZ) A layer of cells that line the inside of the neural tube; contains progenitor cells that divide and give rise to cells of the central nervous system. > subventricular zone (SVZ) A layer of progenitor cells located just inside the ventricular zone; thicker in mammals with large brains. [> symmetrical division Division of a progenitor cell that gives rise to two identical progenitor cells; increases the size of the ventricular zone and hence the brain that develops from it. >> asymmetrical division Division of a progenitor cell that gives rise to another progenitor cell and a neuron, which migrates away from the ventricular zone toward its final resting place in the brain. > radial glia Special glia with fibers that grow radially outward from the ventricular zone to the surface of the cortex; provide guidance for neurons migrating outward during brain development. Migrating neuron Radial glia cell Ventricular zone Earty FIGURE 3.9 Cortical Development This cross section through the cerebral cortex shows it early in its development. The radially oriented fibers of glial cells help to guide the migration of newly formed neurons from the ventricular zone to their final resting place in the cerebral cortex. Each successive wave of neurons passes neurons that migrated earlier, so the most recently formed neurons occupy layers closer to the cortical surface. (Adapted from Rakic, P. Trends in Neuroscience, 1995, 18, 383-388.) 78 Chapter 3 Structure of the Nervous System five layers of neurons, and their migration takes about two weeks. The end of cortical development occurs when the progenitor cells receive a chemical signal that causes them to die—a phenomenon known as apoptosis (literally, a “falling away”). Molecules of the chemical that conveys this signal bind with receptors that activate killer genes within the cells. (All cells have these genes, but only certain cells possess the receptors that respond to the chemical signals that turn them on.) At this time, radial glia are transformed into astrocytes. The brains of the earliest vertebrates were smaller than those of later animals and were simpler as well. The evolutionary process brought about genetic changes that were responsible for the development of more complex brains, with more parts and more interconnections. An important factor in the evolution ofmore complex brains is genetic duplication (Allman, 1999). As Lewis (1992) noted, most of the genes that a species possesses perform important functions. If a mutation causes one of these genes to do something new, the previous function would be lost, and the animal might not survive. However, geneticists have discovered that genes can sometimes du- plicate themselves, and if these duplications occur in cells that give rise to ova or sperms, the duplication can be passed on to the organism's offspring. This means that the offspring will have one gene to perform the important functions and another one to “experiment” with. [fa mutation of the extra gene occurs, the old gene isstill present and its important function is still performed. As we saw in Chapter 1, the human brain is larger than that of any other large animal when corrected for body size—more than three times larger than that of a chimpanzee, our closest relative. What types of genetic changes are required to produce a large brain? Rakic (1988, 2009) suggests that the size differences between these two brains could be caused by a very sim- ple process. We just saw that the size of the ventricular zone increases during symmetrical division of the pro- genitor cells located there. The ultimate size of the brain is determined by the size of the ventricular zone. As Rakic notes, each symmetrical division doubles the number of progenitor cells and thus doubles the size of the brain. The human brain is ten times larger than that of a rhesus macaque monkey. Thus, between three and four addi- tional symmetrical divisions of progenitor cells would account for the difference in the size of these two brains. In fact, the stage of symmetrical division lasts about two days longer in humans, which provides enough time for three more divisions. The period of asymmetrical divi- sion is longer, too, which accounts for the fact that the human cortex is 15 percent thicker. Thus, delays in the termination of the symmetrical and asymmetrical periods of development could be responsible for the increased size of the human brain. A few simple mutations of the genes that control the timing of brain development could be responsible for these delays. The process I have just described explains the devel- opment of the brains of small mammals such as rodents. These brains have a smooth outer surface, which limits the size of the cerebral cortex that cover them. Larger brains, especially those of the larger primates, have con- voluted brains—brains with a surface covered by grooves and bulges. Convolutions greatly increase the surface area of the cerebral cortex, which means that the cortex ofa convoluted brain contains many more neurons than that of a smooth brain. The increased number of neu- rons in the convoluted human cerebral cortex makes possible the complex circuitry found in our brains. “Two studies appear to have discovered an important aspect of the process responsible for the development of convoluted brains. The subventricular zone of convo- luted brains is much thicker than that of smooth brains. In fact, this zone can be divided into two parts, the inner SVZ and the outer SVZ. (The inner SVZ is located closer to the wall of the neural tube, and the outer SVZ is located closer to the surface of the brain.) In smooth- brained animals such as rodents, all of the cells of the brain derive from progenitor cells located in the ven- tricular and subventricular zones. Because the cell bod- es of the radial glia that develop from the progenitor cells are locked in place, the surface of the developing cortex remains more or less parallel to the wall of the neural tube, which means that it will remain smooth. Fietz et al. (2010) and Hansen etal. (2010) found that, during development of the human brain, some new- born progenitor cells migrated into the inner SVZ, po- sitioning themselves between the fibers of the radial glia whose cell bodies were anchored in place. These unat- tached progenitor cells undergo asymmetrical division, sending neurons into the upper layer of the developing cortex. This source of neurons increases the numbers of cells in the cerebral cortex, which forces it to bend and fold into convolutions. The genes that control this pro- cess have not yet been discovered. Once neurons have migrated to their final locations, they begin forming connections with other neurons. They grow dendrites, which receive the terminal buttons from the axons of other neurons, and they grow axons of their own. Some neurons extend their dendrites and ax- ons laterally, connecting adjacent columns of neurons or even establishing connections with other neurons in dis- tant regions of the brain. The growth of axons is guided by physical and chemical factors. Once the growing ends of the axons (the growth cones) reach their targets, they form numerous branches. Each of these branches finds a vacant place on the membrane of the appropriate type of postsynaptic cell, grows a terminal button, and estab- lishes a synaptic connection. Apparently, different types s (ay po toe sis) Death of a cell caused by a chemical signal that activates a genetic mechanism inside the cell.  The Central Nervous System 81 Cerebral cortex (gray matter) Fissure riGURE 3.11 Cross Section of the Human Brain This brain slice shows fissures and gyri and the layer of cerebral cortex that follows these convolutions. is sent to primary sensory cortex of the contralateral hemisphere. Thus, the primary somatosensory cortex of the left hemisphere learns what the right hand is hold- ing, the left primary visual cortex learns what is happen- ing toward the person's right, and so on. The region of the cerebral cortex that is most directly involved in the control of movement is the primary motor cortex, located just in front of the primary somatosensory cortex. Neurons in different parts of the primary motor cortex are connected to muscles in different parts of the body. The connections, like those of the sensory regions of the cerebral cortex, are contralateral; the left primary mo- tor cortex controls the right side of the body and vice versa. “Thus, ifa surgeon places an clectrode on the surface of the primary motor cortex and stimulates the neurons there with a weak electrical current, the result will be movement ofa particular part of the body. Moving the clectrode to a different spot will cause a different part of the body to move. (Look again at Figure 3.12.) 1 like to think of the strip of primary motor cortex as the keyboard of a piano, with cach key controlling a different movement. (We will see shortly who the “player” of this piano is.) The regions of primary sensory and motor cortex occupy only a small part of the cerebral cortex. The rest of the cerebral cortex accomplishes what is done be- tween sensation and action: perceiving, learning and remembering, planning, and acting. These processes take place in the association areas of the cerebral cortex. The central sulcus provides an important dividing line between the rostral and caudal regions of the cerebral cortex. (Look once more at Figure 3.12.) The rostral region is involved in movement-related activities, such as planning and executing behaviors. The caudal region is involved in perceiving and learning. Discussing the various regions of the cerebral cortex is easier if we have names for them. In fact, the cerebral cortex is divided into four arcas, or lobes, named for the bones of the skull that cover them: the frontal lobe, pa- rietal lobe, temporal lobe, and occipital lobe. Of course, the brain contains two of each lobe, one in each hemi- sphere. The frontal lobe (the “front”) includes every- thing in front of the central sulcus. The parietal lobe (the “wall”) is located on the side of the cerebral hemi- sphere, just behind the central sulcus, caudal to the frontal lobe. The temporal lobe (the “temple”) juts for- ward from the base of the brain, ventral to the frontal and parietal lobes. The occipital lobe (from the Latin ob, “im back of” and caput, “head”) lies at the very back of the brain, caudal to the parietal and temporal lobes. > primary motor cortex The region of the posterior frontal lobe that contains neurons that control movements of skeletal muscles. >frontal lobe The anterior portion of the cerebral cortex, rostral to the parietal lobe and dorsal to the temporal lobe. >> parietal lobe (pa rye itul) The region of the cerebral cortex caudal to the frontal lobe and dorsal to the temporal lobe. >> temporal lobe (tem por ul) The region of the cerebral cortex rostral to the occipital lobe and ventral to the parietal and frontal lobes. > eccipital lobe (ok sip i tul) The region of the cerebral cortex caudal to the parietal and temporal lobes. 82 Chapter 3 Structure of the Nervous System Primary motor cortex Insular cortex Primary auditory Central sulcus Portion of Left Hemisphere Primary auditory cortex rIGURE 3.12 The Primary Sensory Regions of the Brain Primary somatosensory cortex Right Hemisphere — Calcarine fissure Left Hemisphere The figure shows a lateral view of the left side of a human brain and part of the inner surface of the right side. The inset shows a cutaway of part of the frontal lobe of the left hemisphere, permitting us to see the primary auditory cortex on the dorsal surface ofthe temporal lobe, which forms the ventral bank of the lateral fissure. Figure 3.13 shows these lobes in three views of the cere- bral hemispheres: a ventral view (a view from the bot- tom), a midsagittal view (a view of the inner surface of the right hemisphere after the left hemisphere has been removed), and a lateral view. (See Figure 3.13.) Each primary sensory area of the cerebral cortex sends information to adjacent regions, called the sensory association cortex. Circuits of neurons in the sensory as- sociation cortex analyze the information received from the primary sensory cortex; perception takes place there, and memories are stored there. The regions of the sen- sory association cortex located closest to the primary sen- sory areas receive information from only one sensory sys- tem. For example, the region closest to the primary visual cortex analyzes visual information and stores visual mem- ories. Regions of the sensory association cortex located far from the primary sensory areas receive information from more than one sensory system; thus, they are involved in several kinds of perceptions and memories. These regions make it possible to integrate information from more than one sensory system. For example, we can Icam the con- nection between the sight of a particular face and the sound ofa particular voice. (Look again at Figure 3.13.) Tf people sustain damage to the somatosensory asso- ciation cortex, their deficits are related to somatosensa- tion and to the environment in general; for example, they may have difficulty perceiving the shapes of objects that they can touch but not see, they may be unable to name paris of their bodies (sec the following case), or they may have trouble drawing maps or following them. Destruction of the primary visual cortex causes blindness. However, although people who sustain damage to the visual association cortex will not become blind, they may be unable to recognize objects by sight. People who sus- tain damage to the auditory association cortex may have difficulty perceiving speech or even producing meaning- ful speech of their own. People who sustain damage to regions of the association cortex at the junction of the three posterior lobes, where the somatosensory, visual, and auditory functions overlap, may have difficulty read- ing or writing. [> sensory association cortex Those regions of the cerebral cortex that receive information from the regions of primary sensory cortex. Mr. M., a city bus driver, stopped to let a passenger climb board. The passenger asked him a question, and Mr. M. suddenly realized that he didn't understand what she was saying. He could hear her, but her words made no sense. He opened his mouth to reply. He made some sounds, but the look on the woman's face told him that she couldn't understand what he was trying to say. He tumed off the engine and looked around at the passengers and tried to tell them to get some help. Although he was unable to say anything, they under- stood that something was wrong, and one of them called an ambulance. An MRI scan showed that Mr. M. had sustained an intracerebral hemorrhage—a kind of stroke caused by rupture of blood vessels in the brain. The stroke had damaged his left parietal lobe. Mr. M. gradually regained the ability to talk and understand the speech of others, but some deficits remained. A colleague, Dr. D., and | studied Mr. M. several weeks after his stroke. The dialogue went something like this: “Show me your hand.” “My hand...my hand.” Looks at his arms, then touches his left forearm. “Show me your chin.” “My chin.” Looks at his arms, looks down, puts his hand on his abdomen. "Show me your right elbow.” “My right...” (points to the right with his right thumb) “elbow.” Looks up and down his right arm, finally touches his right shoulder. As you can see, Mr. M. could understand that we were asking him to point out parts of his body and could repeat the names of the body parts when we spoke them, but he could not identify which body parts these names referred to. This strange deficit, which sometimes follows damage to the left parietal lobe, is called auto- topagnosia, or “poor knowledge of one's own topogra- phy.” (A better term would be autotopanomia, or “poor knowledge of the names of one's own topography," but, then, no one asked me to choose the term.) The parietal lobes are involved with space: the right primarily with external space and the left with one's body and personal space. | will say more about disorders such as this one in Chapter 14, which deals with brain mecha- nisms of language. Just as regions of the sensory association cortex of the posterior part of the brain are involved in perceiv- ing and remembering, the frontal association cortex is involved in the planning and execution of movements. The Central Nervous System 83 Limbic cortex Temporal Lobe Cross section through midbrain Frontal Lobe ai Occipital (a) Lobe Cingulate gyrus (limbic cortex) Parietal Ba Lobe Frontal Lobe Occipital Lobe TemporalLobe (pb) Primary Primary motor cortex Somatosensory cortex Parietal Frontal Lobe Lobe sa a Primary visual cortex Primary aúditory cortex (mostly hidden from view) — Temporal Lobe (0) Rostale-— SS caudal rigurE 3.13 The Four Lobes of the Cerebral Cortex This figure shows the location of the four lobes, the primary sensory and motor cortex, and the association cortex. (a) Ventral view, from the base of the brain. (b) Midsagittal view, with the cerebellum and brain stem removed. (c) Lateral view. 86 Chapter 3 Structure of the Nervous System Massa intermedia Corpus callosum Hippocampus of Cerebellum right hemisphere (ghosted in) rigurE 3.16 The Major Components of the Limbic System All of the left hemisphere except for the limbic system has been removed. Basal Ganglia. The basal ganglia are a collection of subcortical nuclei in the forebrain, which lie beneath the anterior portion of the lateral ventricles. Nuclei are groups of neurons of similar shape. (The word nucleus, from the Greek “nut,” can refer to the inner portion of an atom, to the structure of a cell that contains the chromosomes, and-—as in this case—to a collection of neurons located within the brain.) The major parts of the basal ganglia are the caudate nucleus, the putamen, and the globus pallidus (the “nucleus with a tail,” the “shell,” and the “pale globe”). (See Figure 3.17.) The basal ganglia are involved in the control of movement. For example, Parkinson's disease is caused by degener- ation of certain neurons located in the midbrain that send axons to the caudate nucleus and the putamen. The symptoms of this disease are weakness, tremors, rigidity of the limbs, poor balance, and difficulty in initiating movements. DIENCEPHALON The second major division of the forebrain, the dien- cephalon, is situated between the telencephalon and the mesencephalon; it surrounds the third ventricle. Its two most important structures are the thalamus and the hy- pothalamus. (Sce Figure 3.17.) Thalamus. The thalamus (from the Greek thalamos, “inner chamber”) makes up the dorsal part of the dien- cephalon. It is situated near the middle of the cerebral hemispheres, immediately medial and caudal to the basal ganglia. The thalamus has two lobes, connected by Basal ganglia rigurE 3.17 The Basal Ganglia and Diencephalon The basal ganglia and diencephalon (thalamus and hypothalamus) are ghosted in to a semitransparent brain. a bridge of gray matter called the massa intermedia, which pierces the middle of the third ventricle. (Look again at Figure 3.17.) The massa intermedia is probably not an important structure, because it is absent in the brains of many people. However, it serves as a useful reference point in looking at diagrams of the brain; it appears in Figures 3.4, 3.15, 3.16, and 3.19. Most neural input to the cerebral cortex is received from the thalamus; indeed, much of the cortical surface can be divided into regions that receive projections from specific parts of the thalamus. Projection fibers are sets of axons that arise from cell bodies located in one re- gion of the brain and synapse on neurons located within another region (that is, they project to these regions). The thalamus is divided into several nuclei. Some thalamic nuclei receive sensory information from the sensory systems. The neurons in these nuclei then relay the sensory information to specific sensory projection [> basal ganglia A group of subcortical nuclei in the telencepha- lon, the caudate nucleus, the globus pallidus, and the putamen; important parts of the motor system. [> nueleus (plural: nuclei) An identifiable group of neural cell bodies in the central nervous system. [> diencephalon (dy en seff a lahn) A region of the forebrain surrounding the third ventricle; includes the thalamus and the hypothalamus. i> thalamus The largest portion of the diencephalon, located above the hypothalamus; contains nuclei that project information to specific regions of the cerebral cortex and receive information from it. >> projection fiber An axon of a neuron in one region of the brain whose terminals form synapses with neurons in another region. areas of the cerebral cortex. For example, the lateral geniculate nucleus receives information from the eye and sends axons to the primary visual cortex, and the medial geniculate nucleus receives information from the inner car and sends axons to the primary auditory cortex. Other thalamic nuclei project to specific re- gions of the cerebral cortex, but they do not relay sen- sory information. For example, the ventrolateral nu- cleus receives information from the cerebellum and projects it to the primary motor cortex. Still other nu- clei receive information from one region of the cere- bral cortex and relay it to another region. And as we will see in Chapter 9, several nuclei are involved in controlling the general excitability of the cerebral cor- tex. To accomplish this task, these nuclei have wide- spread projections to all cortical regions. Hypothalamus. As its name implies, the hypothalamus lies at the base of the brain, under the thalamus. Although the hypothalamus is a relatively small struc- ture, it is an important one. It controls the autonomic nervous system and the endocrine system and organizes behaviors related to survival of the species —the so-called four F's: fighting, feeding, flecing, and mating. The hypothalamus is situated on both sides of the ventral portion of the third ventricle. The hypothala- mus is a complex structure, containing many nuclei and fiber tracts. Figure 3.18 indicates its location and size. Note that the pituitary gland is attached to the base of the hypothalamus via the pituitary stalk. Just in front of the pituitary stalk is the optic chiasm, where half of the axons in the optic nerves (from the eyes) cross from one side of the brain to the other. (See Figure 3.18.) The Corpus callosum Hypothalamic nuclei Pituitary Optic chiasm — gland The Central Nervous System 87 role of the hypothalamus in the control of the four F's (and other behaviors, such as drinking and sleeping) will be considered in several chapters later in this book. Much of the endocrine system is controlled by hormones produced by cells in the hypothalamus. À special system of blood vessels directly connecis the hypothalamus with the anterior pituitary gland. (See Figure 3.19.) The hypothalamic hormones are secreted by specialized neurons called neurosecretory cells, located near the base of the pituitary stalk. These hor- mones stimulate the anterior pituitary gland to secrete its hormones. For example, gonadotropin-releasing hormone >> lateral geniculate nucleus A group of cell bodies within the lateral geniculate body of the thalamus that receives fibers from the retina and projects fibers to the primary visual cortex. >> medial geniculate nucleus A group of cell bodies within the medial geniculate body of the thalamus; receives fibers from the auditory system and projects fibers to the primary auditory cortex. > ventrolateral nucleus A nucleus of the thalamus that receives inputs from the cerebellum and sends axons to the primary motor cortex. >> hypothalamus The group of nuclei of the diencephalon situated beneath the thalamus; involved in regulation of the autonomic nervous system, control of the anterior and posterior pituitary glands, and integration of species-typical behaviors. >> optic chiasm (kye az'm) An X-shaped comection between the optic nerves, located below the base of the brain, just anterior to the pituitary gland. > anterior pituitary gland The anterior part of the pituitary gland; an endocrine gland whose secretions are controlled by the hypothalamic hormones. >> neurosecretory cell A neuron that secretes a hormone or hormonelike substance. Massa Wall of third Fornix intermedia ventricle Mammillary ody rigurE 3.18 A Midsagittal View of Part of the Brain This view shows some of the nuclei of the hypothalamus. The nuclei are situated on the far side of the wall of the third ventricle, inside the right hemisphere. 88 Chapter 3 Structure of the Nervous System Neurosecretory cells in the hypothalamus For posterior pituitary gland Pituitary Anterior pituitary gland Secretory cells; release <= anterior pituitary hormones riGurE 3.19 The Pituitary Gland For anterior pituitary gland Mammillary body Capillary bed around terminals of neurosecretory cells; hypothalamic hormones released here Artery Terminals release posterior pituitary hormones. Hormones released by the neurosecretory cells in the hypothalamus enter capillaries and are conveyed to the anterior pituitary gland, where they control its secretion of hormones. The hormones of the posterior pituitary gland are produced in the hypothalamus and carried there in vesicles by means of axoplasmic transport. causes the anterior pituitary gland to secrete the gonado- tropic hormones, which play a role in reproductive physiol- ogy and behavior. Most of the hormones secreted by the anterior pitu- itary gland control other endocrine glands. Because of this function, the anterior pituitary gland has been called the body's “master gland.” For example, the gonado- tropic hormones stimulate the gonads (ovaries and tes- tes) to release male or female sex hormones. These hor- mones affect cells throughout the body, including some in the brain. Two other anterior pituitary hormones— prolactin and somatotropic hormone (growth hor- mone)—do not control other glands but act as the final messenger. The bchavioral effects of many of the ante- rior pituitary hormones are discussed in later chapters. The hypothalamus also produces the hormones of the posterior pituitary gland and controls their secre- tion. These hormones include oxytocin, which stimu- lates ejection of milk and uterine contractions at the time of childbirth, and vasopressin, which regulates urine output by the kidneys. They are produced by neu- rons in the hypothalamus whose axons travel down the pituitary stalk and terminate in the posterior pituitary gland. The hormones are carried in vesicles through the axoplasm of these neurons and collect in the terminal buttons in the posterior pituitary gland. When these axons fire, the hormone contained within their terminal buttons is liberated and enters the circulatory system. The Midbrain The midbrain (also called the mesencephalon) sur- rounds the cerebral aqueduct and consists of two major parts: the tectum and the tegmentum. TECTUM The tectum (“roof”) is located in the dorsal portion of the mesencephalon. Its principal structures are the superior colliculi and the inferior colliculi, which appear as four bumps on the dorsal surface of the brain stem. The brain [> posterior pituitary gland The posterior part of the pituitary gland; an endocrine gland that contains hormone-secreting terminal buttons of axons whose cell bodies lie within the hypothalamus. brain The mesencephalon; the central of the three major divisions of the brain. [> mesencephalon (mezz en seff a lahn) The midbrain; a region of the brain that surrounds the cerebral aqueduct; includes the tectum and the tegmentum. [>tectum The dorsal part of the midbrain; includes the superior and inferior colliculi. [> superior colliculi (ka lik yew lee) Protrusions on top of the midbrain; part of the visual system. >> inferior colliculi Protrusions on top of the midbrain; part of the auditory system. > brain stem The “stem” of the brain, from the medulla to the midbrain, excluding the cerebellum. MYELENCEPHALON The myelencephalon contains one major structure, the medulla oblongata (literally, “oblong marrow”), usually just called the medulla. This structure is the most caudal portion of the brain stem; its lower border is the rostral end of the spinal cord. (Refer again to Figures 3.15 and 3.20a.) The medulla contains part of the reticular forma- tion, including nuclei that control vital functions such as regulation of the cardiovascular system, respiration, and skeletal muscle tonus. The Spinal Cord The spinal cord is a long, conical structure, approximately as thick as our litle finger. The principal function of the spinal cord is to distribute motor fibers to the effector organs of the body (glands and muscles) and to collect somatosensory information to be passed on to the brain. The spinal cord also has a certain degree of autonomy from the brain; various reflexive control circuits (some of which are described in Chapter 8) are located there. The spinal cord is protected by the vertebral column, which is composed of twenty-four individual vertebrae of the cervical (neck), thoracic (chest), and lumbar (lower back) regions and the fused vertebrae that make up the sacral and cocoygeal portions of the column (located in the pelvic region). The spinal cord passes through a hole in cach of the vertebrae (the spinal foramens). Figure 3.21 illustrates the divisions and structures of the spinal cord and vertebral column. (See Figure 3.21.) The spinal cord is only about two-thirds as long as the vertebral column; the rest of the space is filled by a mass of spinal roots composing the cauda equina (“horsc's tail”). (Refer back to Figure 3.3.) Early in embryological development the vertebral column and spinal cord are the same length. As develop- ment progresses, the vertebral column grows faster than the spinal cord. This differential growth rate causes the spinal roots to be displaced downward; the most caudal roots travel the farthest before they emerge through openings between the vertebrae and thus compose the cauda equina. To produce the caudal block that is some- times used in pelvic surgery or childbirth, a local anes- thetic can be injected into the CSF contained within the sac of dura mater surrounding the cauda equina. The drug blocks conduction in the axons of the cauda equina. Figure 3.22(a) shows a portion of the spinal cord, with the layers of the meninges that wrap it. Small bundles of fibers emerge from each side of the spinal cord in two straight lines along its dorsolateral and ventrolateral surfaces. Groups of these bundles fuse together and become the thirty-one paired sets of dorsal roots and ventral roots. The dorsal and ventral roots join together as they pass through the intervertebral foramens and become spinal nerves. (See Figure 3.22a.) The Central Nervous System 91 Cervical vertebrae Spinal foramen ventral (spinal cord passes through €& this opening) Thoracic vertebrae Dorsal Ventral Lumbar z vertebrae Sacral vertebrae Dorsal (fused) Coceyx FIGURE 3.21 Ventral View of the Spinal Column Details show the anatomy of the bony vertebrae. Figure 3.22(b) shows a cross section of the spinal cord. Like the brain, the spinal cord consists of white matter and gray matter. Unlike the brain's, the spinal cord's white matter (consisting of ascending and descend- ing bundles of myelinated axons) is on the outside; the gray matter (mostly neural cell bodies and short, unmy- elinated axons) is on the inside. In Figure 3.22(b), ascending tracts are indicated in blue; descending tracts are indicated in red. (See Figure 3.22b.) > spinal cord The cord of nervous tissue that extends caudally from the medulla. > spinal root A bundie of axons surrounded by connective tissue that occurs in pairs, which fuse and form a spinal nerve. >> cauda equina (ee kwye na) A bundle of spinal roots located caudal to the end of the spinal cord. >> caudal block The anesthesia and paralysis of the lower part of the body produced by injection of a local anesthetic into the cerebrospinal fluid surrounding the cauda equina. > dorsal root The spinal root that contains incoming (afferent) sensory fibers. >ventral root The spinal root that contains outgoing (efferent) motor fibers. 92 Chapter 3 Structure of the Nervous System White matter Gray matter Subarachnoid space Dorsal root ganglion Ventral root Z Dorsal root Spinal nerve, Pia mater (adheres to Spinal cord) Arachnoid membrane Ventral Dorsal (b) Dura mater Nertebra (a) FIGURE 3.22 Ventral View of the Spinal Cord The figure shows (3) a portion of the spinal cord, showing the layers of the meninges and the relationship of the spinal cord to the vertebral column; and (b) a cross section through the spinal cord. Ascending tracts are shown in blue; descending tracts are shown in red. SECTION SUMMARY The brain consists of three major divisions, organized around the three chambers of the tube that develops early in embryonic life: the forebrain, the midbrain, and the hindbrain. The development of the neural tube into the mature central nervous system is illus- trated in Figure 3.8, and Table 3.2 outlines the major divisions and subdivisions of the brain. During the first phase of brain development, sym- metrical division of the progenitor cells of the ventric- ular and subventricular zones, which lines the neural tube, increases in size. During the second phase, asymmetrical division of these cells gives rise to neu- rons, which migrate up the fibers of radial glial cells to their final resting places. There, neurons develop den- drites and axons and establish synaptic connections with other neurons. Later, neurons that fail to develop a sufficient number of synaptic connections are killed The Central Nervous System through apoptosis. Although the basic development of the nervous system is genetically controlled, sen- sory stimulation plays a role in refining the details. In addition, the neural circuitry of even a fully mature brain can be modified through experience. The duplication of genes—in particular, master genes that control groups of other genes —facilitated the increase in complexity of the brain during the pro- cess of evolution. When a gene is duplicated, one of the copies can continue to perform vital functions, leav- ing the other copy for “experimentation” through muta- tions. The large size of the human brain, relative to the brains of other primates, appears to be accomplished primarily by lengthening the first and second periods of brain development, and convolutions are produced by division of progenitor cells of the inner SVZ that are not anchored to the wall of the neural tube. The forebrain, which surrounds the lateral and third ventricles, consists of the telencephalon and diencephalon. The telencephalon contains the cere- bral cortex, the limbic system, and the basal ganglia. The cerebral cortex is organized into the frontal, pari- etal, temporal, and occipital lobes. The central sulcus divides the frontal lobe, which deals specifically with movement and the planning of movement, from the other three lobes, which deal primarily with perceiving and learning. The limbic system, which includes the limbic cortex, the hippocampus, and the amygdala, is involved in emotion, motivation, and learning. The basal ganglia participate in the control of movement. The diencephalon consists of the thalamus, which directs information to and from the cerebral cortex, and the hypothalamus, which controls the endocrine system and modulates species-typical behaviors. The midbrain, which surrounds the cerebral aque- duct, consists of the tectum and the tegmentum. The The Peripheral Nervous System The brain and spinal cord communicate with the rest of the body via the cranial nerves and spinal nerves. These nerves are part of the peripheral nervous system, which conveys sensory information to the central nervous system and conveys messages from the central nervous system to the body's muscles and glands. Spinal Nerves The spinal nerves begin at the junction of the dorsal and ventral roots of the spinal cord. The nerves leave the vertebral column and travel to the muscles or sen- sory receptors they innervate, branching repeatedly as they go. Branches of spinal nerves often follow blood vessels, especially those branches that innervate skeletal muscles. (Refer back to Figure 3.3.) Now let us consider the pathways by which sensory information enters the spinal cord and motor information Icaves it. The cell bodies of all axons that bring sensory information into the brain and spinal cord are located outside the CNS. (The sole exception is the visual system; the retina of the eye is actually a part of the brain.) These incoming axons are referred to as afferent axons because they “bear toward” the CNS. The cell bodies that give rise to the axons that bring somatosensory information to the spinal cord reside in the dorsal root ganglia, rounded swellings of the dorsal root. (See Figure 3.23.) These neu- rons are of the unipolar type (described in Chapter 2). The axonal stalk divides close to the cell body, sending The Peripheral Nervous System 93 tectum is involved in audition and the control of visual reflexes and reactions to moving stimuli. The tegmen- tum contains the reticular formation, which is impor- tant in sleep, arousal, and movement; the periaque- ductal gray matter, which controls various species-typical behaviors; and the red nucleus and the substantia nigra, both parts of the motor system. The hindbrain, which surrounds the fourth ventricle, contains the cerebellum, the pons, and the medulla. The cerebellum plays an important role in integrating and coordinating movements. The pons contains some nuclei that are important in sleep and arousal. The medulla oblongata, too, is involved in sleep and arousal, but it also plays a role in control of move- ment and in control of vital functions such as heart rate, breathing, and blood pressure. The outer part of the spinal cord consists of white matter: axons conveying information up or down. The central gray matter contains cell bodies. one limb into the spinal cord and the other limb out to the sensory organ. Note that all of the axons in the dorsal root convey somatosensory information. Cell bodies that give rise to the ventral root are lo- cated within the gray matter of the spinal cord. The ax- ons of these multipolar neurons leave the spinal cord via a ventral root, which joins a dorsal root to make a spinal nerve. The axons that leave the spinal cord through the ventral roots control muscles and glands. They are re- ferred to as efferent axons because they “bear away from” the CNS. (Look again at Figure 3.23.) Cranial Nerves “Twelve pairs of cranial nerves are attached to the ventral surface of the brain. Most of these nerves serve sensory and motor functions of the head and neck region. One of them, the tenth, or vagus nerve, regulates the functions >> spinal nerve A peripheral nerve attached to the spinal cord. > afferent axon An axon directed toward the central nervous system, conveying sensory information. “> dorsal root ganglion A nodule on a dorsal root that contains cell bodies of afferent spinal nerve neurons. > efferent axon (effur ent) An axon directed away from the central nervous system, conveying motor commands to muscles and glands. >> eranial nerve A peripheral nerve attached directly to the brain. > vagus nerve (vay guss) The largest of the cranial nerves, conveying efferent fibers of the parasympathetic division of the autonomic nervous system to organs of the thoracic and abdominal cavities. 96 Chapter 3 Structure of the Nervous System Note that individual sympathetic ganglia are con- nected to the neighboring ganglia above and below, thus forming the sympathetic ganglion chain. (Sce Figure 3.25.) The axons that leave the spinal cord through the ventral root belong to the preganglionic neurons. Sympathetic preganglionic axons enter the ganglia of the sympathetic chain. Most of the axons form synapses there, but others pass through these ganglia and travel to one of the sympathetic ganglia located among the inter- nal organs. With one exception (mentioned in the next paragraph), all sympathetic preganglionic axons form synapses with neurons located in once of the ganglia. The neurons with which they form synapses are called post- ganglionic neurons. The postganglionic ncurons send axons to the target organs, such as the intestines, stom- ach, kidneys, or sweat glands. (See Figure 3.25.) The sympathetic nervous system controls the adrenal medulla, a set of cells located in the center of the adrenal gland. The adrenal medulla closely resembles a sympa- thetic ganglion. It is innervated by preganglionic axons, and its secretory cells are very similar to postganglionic sympathetic neurons. These cells secrete epinephrine and norepinephrine when they are stimulated. These hor- mones function chiefly as an adjunct to the direct neural effects of sympathetic activity; for example, they increase blood flow to the muscles and cause stored nutrients to be broken down into glucose within skeletal muscle cells, thus increasing the energy available to these cells. The terminal buttons of sympathetic preganglionic axons secrete acetylcholine. The terminal buttons on the target organs, belonging to the postganglionic axons, secrete another neurotransmitter: norepineph- rine. (An exception to this rule is provided by the sweat glands, which are innervated by acetylcholine-secreting terminal buttons.) PARASYMPATHETIC DIVISION OF THE ANS The parasympathetic division of the autonomic nervous system supports activities that are involved with increases in the body's supply of stored energy. These activities include salivation, gastric and intestinal motility, secretion of digestive juices, and increased blood flow to the gastro- intestinal system. Cell bodies that give rise to preganglionic axons in the parasympathetic nervous system are located in two regions: the nuclei of some of the cranial nerves (espe- cially the vagus nerve) and the intermediate hom of the gray matter in the sacral region of the spinal cord. Thus, the parasympathetic division of the ANS has often been referred to as the craniosacral system. Parasympathetic gan- glia are located in the immediate vicinity of the target organs; the postganglionic fibers are therefore relatively short. The terminal buttons of both preganglionic and postganglionic neurons in the parasympathetic nervous system secrete acetylcholine. Table 3.3 summarizes the major divisions of the peripheral nervous system. (> sympathetic ganglion ch: One of a pair of groups of sympathetic ganglia that lie ventrolateral to the vertebral column. > preganglionic neuron The efferent neuron of the autonomic nervous system whose cell body is located in a cranial nerve nucleus or in the intermediate horn of the spinal gray matter and whose terminal buttons synapse upon postganglionic neurons in the autonomic ganglia. [> postganglionic neuron Neurons of the autonomic nervous system that form synapses directly with their target organ. > adrenal medulla The inner portion of the adrenal gland, located atop the kidney, controlled by sympathetic nerve fibers; secretes epinephrine and norepinephrine. [> parasympathetic division The portion of the autonomic nervous system that controls functions that occur during a relaxed state. Spinal Nerves Afferents from sense organs Efferents to muscles Cranial Nerves Afferents from sense organs Efferenis to muscles TABLE 3.3 The Major Divisions of the Peripheral Nervous System Sympathetic Branch Spinal nerves (from thoracic and lumbar regions) Sympathetic ganglia Parasympathetic Branch Cranial nerves (3rd, 7th, 9th, and 10th) Spinal nerves (from sacral region) Parasympathetic ganglia (adjacent to target organs) The Peripheral Nervous System 97 Dilates pupil, Constricts pupil, inhibits tears produces tears Inhibits salivation Stimulates salivation Constricts ainvays <s ungs Speeds Ema heartbeat heartbeat Stimulates sweating 1) Stimulates “ glucose sz ã release ver H 55 £ By Quê, a EE Es ! Constricts blood >E Es vessels in skin Pancreas sç Ss to Ê A —+ Anhibits 1 digestive Stimulates e— system digestive e— Stomach system e— Stimulates secretion of epinephrine and norepinephrine by adrenal X Large intestine medula Small intestine <—s Contracts É Relaxes bladder NE bladder Parasympathetic: Preganglionic neuron e Postganglionic neuron e——> sº Stimulates Sympathetic: sexual Preganglionic neuron €-——< Stimulates arousal Postganglionic neuron e— > orgasm FIGURE 3.25 The Autonomic Nervous System The schematic figure shows the target organs and functions served by the sympathetic and parasympathetic branches of the autonomic nervous system.  98 Chapter 3 Explore the Virtual Brain in MyPsychLab SECTION SUMMARY The spinal nerves and the cranial nerves convey sensory which controls activities that occur during relaxation, axons into the central nervous system and motor axons such as decreased heart rate and increased activity of out from it. Spinal nerves are formed by the junctions of the digestive system. The pathways of the autonomic the dorsal roots, which contain incoming (afferent) nervous system contain preganglionic axons, from the axons, and the ventral roots, which contain outgoing brain or spinal cord to the sympathetic or parasympa- (efferent) axons. The autonomic nervous system consists thetic ganglia, and postganglionic axons, from the gan- of two divisions: the sympathetic division, which controls glia to the target organ. The adrenal medulla, which activities that occur during excitement or exertion, such secretes epinephrine and norepinephrine, is controlled as increased heart rate, and the parasympathetic division, by axons of the sympathetic nervous system. Review Questions e-[ Study and Review on MyPsychLab 1. Explain the origins of the names of brain structures and the 4. Describe the telencephalon, one of the two major terms used to indicate directions and planes of section. structures of the forebrain. 2. Describe the blood supply to the brain, the menin- 5. Describe the two major structures of the diencephalon. ges, the ventricular system, and flow of cerebrospinal 6, Describe the tuo major structures of the midbrain, the fluid through the brain and its production. two major structures of the hindbrain, and the spinal cord. 3. Outline the development of the central nervous 7 - Describe the peripheral nervous system, including the system and the evolution of the human brain. two divisions of the autonomic nervous system. Explore the Virtual Brain in MyPsychLab m THE NERVOUS SYSTEM In order to understand the function of the nervous system, one must first leam its structure and its development. The virtual brain includes two modules that will help you master the material. The Development of the Nervous System module shows the major division of the brain. The Nervous System module that will help you become familiar with the names and locations of more specific structures (e.g. the ventricles) and brain regions. CNE A RO NOR ND VE GERDETOS (Fianesoisecion ADERIR [RT