Neuroscience - Exploring the Brain - The Structure of the Nervous System PDF

 CHAPTER SEVEN The Structure of the Nervous System INTRODUCTION GROSS ORGANIZATION OF THE MAMMALIAN NERVOUS SYSTEM Anatomical References The Central Nervous System The Cerebrum...

 CHAPTER SEVEN The Structure of the Nervous System INTRODUCTION GROSS ORGANIZATION OF THE MAMMALIAN NERVOUS SYSTEM Anatomical References The Central Nervous System The Cerebrum The Cerebellum The Brain Stem The Spinal Cord The Peripheral Nervous System The Somatic PNS The Visceral PNS Afferent and Efferent Axons The Cranial Nerves The Meninges The Ventricular System BOX 7.1 OF SPECIAL INTEREST: Water on the Brain New Views of the Brain Imaging the Structure of the Living Brain BOX 7.2 BRAIN FOOD: Magnetic Resonance Imaging Functional Brain Imaging BOX 7.3 BRAIN FOOD: PET and fMRI UNDERSTANDING CNS STRUCTURE THROUGH DEVELOPMENT Formation of the Neural Tube BOX 7.4 OF SPECIAL INTEREST: Nutrition and the Neural Tube Three Primary Brain Vesicles Differentiation of the Forebrain Differentiation of the Telencephalon and Diencephalon Forebrain Structure-Function Relationships Differentiation of the Midbrain Midbrain Structure-Function Relationships Differentiation of the Hindbrain Hindbrain Structure-Function Relationships Differentiation of the Spinal Cord Spinal Cord Structure-Function Relationships Putting the Pieces Together Special Features of the Human CNS A GUIDE TO THE CEREBRAL CORTEX Types of Cerebral Cortex Areas of Neocortex Neocortical Evolution and Structure-Function Relationships BOX 7.5 PATH OF DISCOVERY: Connecting with the Connectome, by Sebastian Seung CONCLUDING REMARKS APPENDIX: AN ILLUSTRATED GUIDE TO HUMAN NEUROANATOMY 179 17 179 179–218_Bear_07_revised_final.indd 179 12/20/14 4:05 AM  180 PART ONE FOUNDATIONS INTRODUCTION INTRODUC CTION In previous chapters, we saw how individual neurons function and com- municate. Now we are ready to assemble them into a nervous system that sees, hears, feels, moves, remembers, and dreams. Just as an un- derstanding of neuronal structure is necessary for understanding neuro- nal function, we must understand nervous system structure in order to understand brain function. Neuroanatomy has challenged generations of students—and for good reason: The human brain is extremely complicated. However, our brain is merely a variation on a plan that is common to the brains of all mammals (Figure 7.1). The human brain appears complicated because it is distorted as a result of the selective growth of some parts within the confines of the skull. But once the basic mammalian plan is understood, these specializa- tions of the human brain become clear. We begin by introducing the general organization of the mammalian brain and the terms used to describe it. Then we take a look at how the three-dimensional structure of the brain arises during embryological and fetal development. Following the course of development makes it easier to understand how the parts of the adult brain fit together. Finally, we explore the cerebral neocortex, a structure that is unique to mammals and proportionately the largest in humans. An Illustrated Guide to Human Neuroanatomy follows the chapter as an appendix. The neuroanatomy presented in this chapter provides the canvas on which we will paint the sensory and motor systems in Chapters 8–14. Because you will encounter a lot of new terms, self-quizzes within this chapter provide an opportunity for review. GROS GROSS SS OR ORGANIZATION RGANIZATION OF THE MAMMALIAN MAMMMALIAN NERVOUS SYSTEM The nervous system of all mammals has two divisions: the central ner- vous system (CNS) and the peripheral nervous system (PNS). Here we identify some of the important components of the CNS and the PNS. We also discuss the membranes that surround the brain and the fluid-filled ventricles within the brain. We’ll then explore some new methods of ex- amining the structure of the brain. But first, we need to review some anatomical terminology. Anatomical References Getting to know your way around the brain is like getting to know your way around a city. To describe your location in the city, you would use points of reference such as north, south, east, and west and up and down. The same is true for the brain, except that the terms—called anatomical references—are different. Consider the nervous system of a rat (Figure 7.2a). We begin with the rat because it is a simplified version that has all the general features of mammalian nervous system organization. In the head lies the brain, and the spinal cord runs down inside the backbone toward the tail. The direc- tion, or anatomical reference, pointing toward the rat’s nose is known as anterior or rostral (from the Latin for “beak”). The direction pointing toward the rat’s tail is posterior or caudal (from the Latin for “tail”). The direction pointing up is known as dorsal (from the Latin for “back”), and the direction pointing down is ventral (from the Latin for “belly”). 179–218_Bear_07_revised_final.indd 180 12/20/14 4:05 AM  CHAPTER 7 THE STRUCTURE OF THE NERVOUS SYSTEM 181 Rat Rabbit 1 cm Rat Cat Rabbit Sheep Cat Dolphin Sheep Chimpanzee Chimpanzee Human Human Dolphin ▲ FIGURE 7.1 Mammalian brains. Despite differences in complexity, the brains of all these spe- cies have many features in common. The brains have been drawn to appear ap- proximately the same size; their relative sizes are shown in the inset on the left. 179–218_Bear_07_revised_final.indd 181 12/20/14 4:05 AM  182 PART ONE FOUNDATIONS Spinal cord Dorsal Spinal Lateral Brain cord Brain Midline Anterior Posterior or rostral or caudal Medial (a) Ventral (b) ▲ FIGURE 7.2 Basic anatomical references in the nervous system of a rat. (a) Side view. Thus, the rat spinal cord runs anterior to posterior. The top side of the (b) Top view. spinal cord is the dorsal side, and the bottom side is the ventral side. If we look down on the nervous system, we see that it may be divided into two equal halves (Figure 7.2b). The right side of the brain and spinal cord is the mirror image of the left side. This characteristic is known as bilateral symmetry. With just a few exceptions, most structures within the nervous system come in pairs, one on the right side and the other on the left. The invisible line running down the middle of the nervous system is called the midline, and this gives us another way to describe anatomi- cal references. Structures closer to the midline are medial; structures farther away from the midline are lateral. In other words, the nose is medial to the eyes, the eyes are medial to the ears, and so on. In addi- tion, two structures that are on the same side are said to be ipsilateral to each other; for example, the right ear is ipsilateral to the right eye. If the structures are on opposite sides of the midline, they are said to be contralateral to each other; the right ear is contralateral to the left ear. To view the internal structure of the brain, it is usually necessary to slice it up. In the language of anatomists, a slice is called a section; to slice al Caud is to section. Although one could imagine an infinite number of ways we might cut into the brain, the standard approach is to make cuts parallel ral Rost to one of the three anatomical planes of section. The plane of the section resulting from splitting the brain into equal right and left halves is called the midsagittal plane (Figure 7.3a). Sections parallel to the midsagittal plane are in the sagittal plane. (a) Midsagittal The two other anatomical planes are perpendicular to the sagittal plane and to one another. The horizontal plane is parallel to the ground (Figure 7.3b). A single section in this plane could pass through both the eyes and the ears. Thus, horizontal sections split the brain into dorsal and ventral parts. The coronal plane is perpendicular to the ground and to the sagittal plane (Figure 7.3c). A single section in this plane could pass through both eyes or both ears but not through all four at the same time. Thus, the coronal plane splits the brain into anterior and posterior parts. (b) Horizontal SELF- SELF F-QUIZ Take a few moments right now and be sure you understand the meaning of these terms: (c) Coronal anterior dorsal lateral sagittal plane rostral ventral ipsilateral horizontal plane posterior midline contralateral coronal plane ▲ FIGURE 7.3 caudal medial midsagittal plane Anatomical planes of section. 179–218_Bear_07_revised_final.indd 182 12/20/14 4:05 AM  CHAPTER 7 THE STRUCTURE OF THE NERVOUS SYSTEM 183 The Central Nervous System The central nervous system (CNS) consists of the parts of the nervous system that are encased in bone: the brain and the spinal cord. The brain lies entirely within the skull. A side view of the rat brain reveals three parts that are common to all mammals: the cerebrum, the cerebel- lum, and the brain stem (Figure 7.4a). The Cerebrum. The rostral-most and largest part of the brain is the cerebrum. Figure 7.4b shows the rat cerebrum as it appears when viewed from above. Notice that it is clearly split down the middle into two cerebral hemispheres, separated by the deep sagittal fissure. In general, the right cerebral hemisphere receives sensations from, and controls movements of, the left side of the body. Similarly, the left cerebral hemisphere is concerned with sensations and movements on the right side of the body. The Cerebellum. Lying behind the cerebrum is the cerebellum (the word is derived from the Latin for “little brain”). While the cerebellum is in fact dwarfed by the large cerebrum, it actually contains as many neu- rons as both cerebral hemispheres combined. The cerebellum is primarily a movement control center that has extensive connections with the cere- brum and the spinal cord. In contrast to the cerebral hemispheres, the left side of the cerebellum is concerned with movements of the left side of the body, and the right side of the cerebellum is concerned with movements of the right side. The Brain Stem. The remaining part of the brain is the brain stem, best observed in a midsagittal view of the brain (Figure 7.4c). The brain stem forms the stalk from which the cerebral hemispheres and the cerebellum sprout. The brain stem is a complex nexus of fibers and cells that in part serves to relay information from the cerebrum to the spinal cord and cer- ebellum, and vice versa. However, the brain stem is also the site where vital functions are regulated, such as breathing, consciousness, and the control of body temperature. Indeed, while the brain stem is considered the most primitive part of the mammalian brain, it is also the most im- portant to life. One can survive damage to the cerebrum and cerebellum, but damage to the brain stem is usually fatal. The Spinal Cord. The spinal cord is encased in the bony vertebral column and is attached to the brain stem. The spinal cord is the major conduit of Side (lateral) Midsagittal view: view: (a) (c) Brain stem Cerebrum Spinal Cerebellum Brain cord stem Right cerebral Top (dorsal) hemisphere view: Left cerebral (b) hemisphere ▲ FIGURE 7.4 Sagittal The brain of a rat. (a) Side (lateral) view. fissure (b) Top (dorsal) view. (c) Midsagittal view. 179–218_Bear_07_revised_final.indd 183 12/20/14 4:05 AM  184 PART ONE FOUNDATIONS Dorsal root Dorsal ganglia roots Spinal Ventral nerves roots ▲ FIGURE 7.5 The spinal cord. The spinal cord runs inside the vertebral column. Axons enter and exit the spinal cord via the dorsal and ventral roots, respectively. These roots come together to form the spinal nerves that course through the body. information from the skin, joints, and muscles of the body to the brain, and vice versa. A transection of the spinal cord results in anesthesia (lack of feeling) in the skin and paralysis of the muscles in parts of the body caudal to the cut. Paralysis in this case does not mean that the muscles cannot function, but they cannot be controlled by the brain. The spinal cord communicates with the body via the spinal nerves, which are part of the peripheral nervous system (discussed below). Spinal nerves exit the spinal cord through notches between each vertebra of the vertebral column. Each spinal nerve attaches to the spinal cord by means of two branches, the dorsal root and the ventral root (Figure 7.5). Recall from Chapter 1 that François Magendie showed that the dorsal root contains axons bringing information into the spinal cord, such as those that signal the accidental entry of a thumbtack into your foot (see Figure 3.1). Charles Bell showed that the ventral root contains axons car- rying information away from the spinal cord—for example, to the muscles that jerk your foot away in response to the pain of the thumbtack. The Peripheral Nervous System All the parts of the nervous system other than the brain and spinal cord comprise the peripheral nervous system (PNS). The PNS has two parts: the somatic PNS and the visceral PNS. The Somatic PNS. All the spinal nerves that innervate the skin, the joints, and the muscles that are under voluntary control are part of the somatic PNS. The somatic motor axons, which command muscle contraction, de- rive from motor neurons in the ventral spinal cord. The cell bodies of the motor neurons lie within the CNS, but their axons are mostly in the PNS. The somatic sensory axons, which innervate and collect information from the skin, muscles, and joints, enter the spinal cord via the dor- sal roots. The cell bodies of these neurons lie outside the spinal cord in 179–218_Bear_07_revised_final.indd 184 12/20/14 4:05 AM  CHAPTER 7 THE STRUCTURE OF THE NERVOUS SYSTEM 185 clusters called dorsal root ganglia. There is a dorsal root ganglion for each spinal nerve (see Figure 7.5). The Visceral PNS. The visceral PNS, also called the involuntary, vegeta- tive, or autonomic nervous system (ANS), consists of the neurons that innervate the internal organs, blood vessels, and glands. Visceral sensory axons bring information about visceral function to the CNS, such as the pressure and oxygen content of the blood in the arteries. Visceral motor fibers command the contraction and relaxation of muscles that form the walls of the intestines and the blood vessels (called smooth muscles), the rate of cardiac muscle contraction, and the secretory function of various glands. For example, the visceral PNS controls blood pressure by regulat- ing the heart rate and the diameter of the blood vessels. We will return to the structure and function of the ANS in Chapter 15. For now, remember that when one speaks of an emotional reaction that is beyond voluntary control—like “butterflies in the stomach” or blushing— it usually is mediated by the visceral PNS (the ANS). Afferent and Efferent Axons. Our discussion of the PNS is a good place to introduce two terms that are used to describe axons in the nervous sys- tem. Derived from the Latin, afferent (“carry to”) and efferent (“carry from”) indicate whether the axons are transporting information toward or away from a particular point. Consider the axons in the PNS relative to a point of reference in the CNS. The somatic or visceral sensory axons bringing information into the CNS are afferents. The axons that emerge from the CNS to innervate the muscles and glands are efferents. The Cranial Nerves In addition to the nerves that arise from the spinal cord and innervate the body, there are 12 pairs of cranial nerves that arise from the brain stem and innervate (mostly) the head. Each cranial nerve has a name and a number associated with it (originally numbered by Galen, about 1800 years ago, from anterior to posterior). Some of the cranial nerves are part of the CNS, others are part of the somatic PNS, and still others are part of the visceral PNS. Many cranial nerves contain a complex mixture of axons that perform different functions. The cranial nerves and their various functions are summarized in the chapter appendix. The Meninges The CNS, that part of the nervous system encased in the skull and verte- bral column, does not come in direct contact with the overlying bone. It is protected by three membranes collectively called the meninges (singular: meninx), from the Greek for “covering.” The three membranes are the dura mater, the arachnoid membrane, and the pia mater (Figure 7.6). The outermost covering is the dura mater, from the Latin words mean- ing “hard mother,” an accurate description of the dura’s leatherlike con- sistency. The dura forms a tough, inelastic bag that surrounds the brain and spinal cord. Just under the dura lies the arachnoid membrane (from the Greek for “spider”). This meningeal layer has an appearance and a consistency resembling a spider web. While there normally is no space between the dura and the arachnoid, if the blood vessels passing through the dura are ruptured, blood can collect here and form what is called a subdural hematoma. The buildup of fluid in this subdural space can disrupt brain function by compressing parts of the CNS. The disorder is treated by drilling a hole in the skull and draining the blood. 179–218_Bear_07_revised_final.indd 185 12/20/14 4:05 AM  186 PART ONE FOUNDATIONS Dura mater Subdural space Arachnoid membrane Subarachnoid space Pia mater Artery Brain (a) (b) ▲ FIGURE 7.6 The meninges. (a) The skull has been removed to show the tough outer menin- geal membrane, the dura mater. (Source: Gluhbegoric and Williams, 1980.) (b) Illustrated in cross section, the three meningeal layers protecting the brain and spinal cord are the dura mater, the arachnoid membrane, and the pia mater. The pia mater, the “gentle mother,” is a thin membrane that adheres closely to the surface of the brain. Along the pia run many blood vessels that ultimately dive into the substance of the underlying brain. The pia is separated from the arachnoid by a fluid-filled space. This subarachnoid Choroid Subarachnoid plexus space space is filled with salty clear liquid called cerebrospinal fluid (CSF). Thus, in a sense, the brain floats inside the head in this thin layer of CSF. Rostral The Ventricular System In Chapter 1, we noted that the brain is hollow. The fluid-filled caverns and canals inside the brain constitute the ventricular system. The fluid that runs in this system is CSF, the same as the fluid in the subarachnoid space. CSF is produced by a special tissue, called the choroid plexus, in the ventricles of the cerebral hemispheres. CSF flows from the paired ventricles of the cerebrum to a series of connected, central cavities at the core of the brain stem (Figure 7.7). CSF exits the ventricular system and enters the subarachnoid space by way of small openings, or aper- tures, located near where the cerebellum attaches to the brain stem. In the subarachnoid space, CSF is absorbed by the blood vessels at special structures called arachnoid villi. If the normal flow of CSF is disrupted, brain damage can result (Box 7.1). Ventricles Caudal in brain We will return to fill in some details about the ventricular system in a moment. As we will see, understanding the organization of the ventricu- lar system holds the key to understanding how the mammalian brain is ▲ FIGURE 7.7 organized. The ventricular system in a rat brain. CSF is produced in the ventricles of the New Views of the Brain paired cerebral hemispheres and flows through a series of central ventricles at For centuries, anatomists have investigated the internal structure of the core of the brain stem. CSF escapes the brain by removing it from the skull, sectioning it in various planes, into the subarachnoid space via small apertures near the base of the cerebel- staining the sections, and examining the stained sections. Much has been lum. In the subarachnoid space, CSF is learned by this approach, but there are some limitations. Among these absorbed into the blood. are the challenges of seeing how parts deep in the brain fit together in 179–218_Bear_07_revised_final.indd 186 12/20/14 4:05 AM  CHAPTER 7 THE STRUCTURE OF THE NERVOUS SYSTEM 187 BOX 7.1 OF SPECIAL INTEREST Water on the Brain I f the flow of CSF from the choroid plexus through the ven- tricular system to the subarachnoid space is impaired, the fluid will back up and cause a swelling of the ventricles. This condition is called hydrocephalus, a term originally meaning Tube inserted into “water head.” lateral ventricle through hole in Occasionally, babies are born with hydrocephalus. skull However, because the skull is soft and not completely formed, the head will expand in response to the increased intracranial fluid, sparing the brain from damage. Often this condition goes unnoticed until the size of the head reaches enormous proportions. In adults, hydrocephalus is a much more serious situ- ation because the skull cannot expand, and intracranial pressure increases as a result. The soft brain tissue is then compressed, impairing function and leading to death if left untreated. Typically, this “obstructive” hydrocephalus is also accompanied by severe headache, caused by the distention of nerve endings in the meninges. Treatment consists of in- Drainage tube, usually introduced serting a tube into the swollen ventricle and draining off the into peritoneal cavity, excess fluid (Figure A). with extra length to allow for growth of child Figure A three dimensions. A breakthrough occurred in 2013 when researchers at Stanford University introduced a new method, called CLARITY, which allows visualization of deep structures without sectioning the brain. The trick is to soak the brain in a solution that replaces light-absorbing lip- ids with a water-soluble gel that turns the brain transparent. If such a “clarified” brain contains neurons that are labeled with fluorescent molecules, such as green fluorescent protein (GFP; see Chapter 2), then appropriate illumination will reveal the location of these cells deep inside the brain (Figure 7.8). ▲ FIGURE 7.8 A method to turn the brain transpar- ent and visualize fluorescent neurons deep in the brain. (a) A mouse brain viewed from above. (b) The same brain rendered transparent by replacing lipids with a water-soluble gel. (c) The trans- parent brain illuminated to evoke fluores- cence from neurons that express green fluorescent protein. (Source: Courtesy of Dr. Kwanghun Chung, Massachusetts Institute of Technology. Adapted from (a) (b) (c) Chung and Deisseroth. 2013, Figure 2.) 179–218_Bear_07_revised_final.indd 187 12/20/14 4:05 AM  188 PART ONE FOUNDATIONS Of course, a clarified brain is still a dead brain. This, to say the least, limits the usefulness of such anatomical methods for diagnosing neu- rological disorders in living individuals. Thus, it is no exaggeration to say that neuroanatomy was revolutionized by the introduction of several methods that enable one to produce images of the living brain. Here we briefly introduce them. Imaging the Structure of the Living Brain. Some types of electromagnetic radiation, like X-rays, penetrate the body and are absorbed by various radiopaque tissues. Thus, using X-ray-sensitive film, one can make two- dimensional images of the shadows formed by the radiopaque structures within the body. This technique works well for the bones of the skull, but not for the brain. The brain is a complex three-dimensional volume of slight and varying radiopacity, so little information can be gleaned from a single two-dimensional X-ray image. An ingenious solution, called computed tomography (CT), was de- veloped by Godfrey Hounsfields and Allan Cormack, who shared the Nobel Prize in 1979. The goal of CT is to generate an image of a slice of brain. (The word tomography is derived from the Greek for “cut.”) To accomplish this, an X-ray source is rotated around the head within the plane of the desired cross section. On the other side of the head, in the trajectory of the X-ray beam, are sensitive electronic sensors of X-irradiation. The information about relative radiopacity obtained with different viewing angles is fed to a computer that executes a mathematical algorithm on the data. The end result is a digital recon- struction of the position and amount of radiopaque material within the plane of the slice. CT scans noninvasively revealed, for the first time, the gross organization of gray and white matter, and the position of the ventricles, in the living brain. While still used widely, CT is gradually being replaced by a newer imaging method, called magnetic resonance imaging (MRI). The advan- tages of MRI are that it yields a much more detailed map of the brain than CT, it does not require X-irradiation, and images of brain slices can be made in any plane desired. MRI uses information about how hydrogen atoms in the brain respond to perturbations of a strong mag- netic field (Box 7.2). The electromagnetic signals emitted by the atoms are detected by an array of sensors around the head and fed to a power- ful computer that constructs a map of the brain. The information from an MRI scan can be used to build a strikingly detailed image of the whole brain. Another application of MRI, called diffusion tensor imaging (DTI), enables visualization of large bundles of axons in the brain. By compar- ing the position of the hydrogen atoms in water molecules at discrete time intervals, the diffusion of water in the brain can be measured. Water dif- fuses much more readily alongside axon membranes than across them, and this difference can be used to detect axon bundles that connect differ- ent regions of the brain (Figure 7.9). ▲ FIGURE 7.9 Diffusion tensor imaging of the human brain. Displayed is a computer recon- Functional Brain Imaging. CT and MRI are extremely valuable for detect- struction of axon bundles in a living hu- ing structural changes in the living brain, such as brain swelling after man brain viewed from the side. Anterior a head injury and brain tumors. Nonetheless, much of what goes on in is to the left. The bundles are pseudo- the brain—healthy or diseased—is chemical and electrical in nature and colored based on the direction of water diffusion. (Source: Courtesy of not observable by simple inspection of the brain’s anatomy. Amazingly, Dr. Satrajit Ghosh, Massachusetts however, even these secrets are beginning to yield to the newest imaging Institute of Technology.) techniques. 179–218_Bear_07_revised_final.indd 188 12/20/14 4:05 AM  CHAPTER 7 THE STRUCTURE OF THE NERVOUS SYSTEM 189 BOX 7.2 BRAIN FOOD Magnetic Resonance Imaging M agnetic resonance imaging (MRI) is a general technique that can be used for determining the amount of certain atoms If we used the procedure discussed earlier, we would simply get a measurement of the total amount of hydrogen at different locations in the body. It has become an important in the head. However, it is possible to measure hydrogen tool in neuroscience because it can be used noninvasively to amounts at a fine spatial scale by taking advantage of the obtain a detailed picture of the nervous system, particularly fact that the frequency at which protons emit energy is pro- the brain. portional to the size of the magnetic field. In the MRI ma- In the most common form of MRI, the hydrogen atoms are chines used in hospitals, the magnetic fields vary from one quantified—for instance, those located in water or fat in the side of the magnet to the other. This gives a spatial code brain. An important fact of physics is that when a hydrogen to the radio waves emitted by the protons: High-frequency atom is put in a magnetic field, its nucleus (which consists of signals come from hydrogen atoms near the strong side of a single proton) can exist in either of two states: a high-energy the magnet, and low-frequency signals come from the weak state or a low-energy state. Because hydrogen atoms are side of the magnet. abundant in the brain, there are many protons in each state. The last step in the MRI process is to orient the gradient of The key to MRI is making the protons jump from one state the magnet at many different angles relative to the head and to the other. Energy is added to the protons by passing an measure the amount of hydrogen. It takes about 15 minutes electromagnetic wave (i.e., a radio signal) through the head to make all the measurements for a typical brain scan. A so- while it is positioned between the poles of a large magnet. phisticated computer program is then used to make a single When the radio signal is set at just the right frequency, the image from the measurements, resulting in a picture of the protons in the low-energy state will absorb energy from the distribution of hydrogen atoms in the head. signal and hop to the high-energy state. The frequency at Figure A is an MRI image of a lateral view of the brain in which the protons absorb energy is called the resonant fre- a living human. In Figure B, another MRI image, a slice has quency (hence the name magnetic resonance). When the been made in the brain. Notice how clearly you can see the radio signal is turned off, some of the protons fall back down white and gray matter. This differentiation makes it possible to the low-energy state, thereby emitting a radio signal of to see the effects of demyelinating diseases on white mat- their own at a particular frequency. This signal can be picked ter in the brain. MRI images also reveal lesions in the brain up by a radio receiver. The stronger the signal, the more because tumors and inflammation generally increase the hydrogen atoms between the poles of the magnet. amount of extracellular water. Central sulcus Cerebellum Figure A Figure B 179–218_Bear_07_revised_final.indd 189 12/20/14 4:05 AM  190 PART ONE FOUNDATIONS BOX 7.3 BRAIN FOOD PET and fMRI U ntil recently, “mind reading” has been beyond the reach of science. However, with the introduction of positron emis- various sites in the brain can be calculated. Compiling these measurements produces an image of the brain activity pat- sion tomography (PET) and functional magnetic resonance tern. The researcher monitors brain activity while the subject imaging (fMRI), it is now possible to observe and measure performs a task, such as moving a finger or reading aloud. changes in brain activity associated with the planning and Different tasks “light up” different brain areas. In order to ob- execution of specific tasks. tain a picture of the activity induced by a particular behavioral PET imaging was developed in the 1970s by two groups or thought task, a subtraction technique is used. Even in the of physicists, one at Washington University led by M. M. Ter- absence of any sensory stimulation, the PET image will con- Pogossian and M. E. Phelps, and a second at UCLA led by tain a great deal of brain activity. To create an image of the Z. H. Cho. The basic procedure is very simple. A radioac- brain activity resulting from a specific task, such as a person tive solution containing atoms that emit positrons (posi- looking at a picture, this background activity is subtracted tively charged electrons) is introduced into the bloodstream. out (Figure B). Positrons, emitted wherever the blood goes, interact with Although PET imaging has proven to be a valuable tech- electrons to produce photons of electromagnetic radiation. nique, it has significant limitations. Because the spatial resolu- The locations of the positron-emitting atoms are found by de- tion is only 5–10 mm3, the images show the activity of many tectors that pick up the photons. thousands of cells. Also, a single PET brain scan may take one One powerful application of PET is the measurement of to several minutes to obtain. This, along with concerns about metabolic activity in the brain. In a technique developed by radiation exposure, limits the number of scans that can be ob- Louis Sokoloff and his colleagues at the National Institute tained from one person in a reasonable time period. Thus, the of Mental Health, a positron-emitting isotope of fluorine or work of S. Ogawa at Bell Labs, showing that MRI techniques oxygen is attached to 2-deoxyglucose (2-DG). This radioac- could be used to measure local changes in blood oxygen lev- tive 2-DG is injected into the bloodstream and travels to the els that result from brain activity, was an important advance. brain. Metabolically active neurons, which normally use glu- The fMRI method takes advantage of the fact that oxyhe- cose, also take up the 2-DG. The 2-DG is phosphorylated by moglobin (the oxygenated from of hemoglobin in the blood) enzymes inside the neuron, and this modification prevents has a magnetic resonance different from that of deoxyhemo- the 2-DG from leaving. Thus, the amount of radioactive 2-DG globin (hemoglobin that has donated its oxygen). More ac- accumulated in a neuron and the number of positron emis- tive regions of the brain receive more blood, and this blood sions indicate the level of neuronal metabolic activity. donates more of its oxygen. Functional MRI detects the loca- In a typical PET application, a person’s head is placed tions of increased neural activity by measuring the ratio of in an apparatus surrounded by detectors (Figure A). Using oxyhemoglobin to deoxyhemoglobin. It has emerged as the computer algorithms, the photons (resulting from positron method of choice for functional brain imaging because the emissions) reaching each of the detectors are recorded. With scans can be made rapidly (50 msec), they have good spatial this information, levels of activity for populations of neurons at resolution (3 mm3), and they are completely noninvasive. The two “functional imaging” techniques now in widespread use are positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). While the technical details differ, both methods detect changes in regional blood flow and metabolism within the brain (Box 7.3). The basic principle is simple. Neurons that are active demand more glu- cose and oxygen. The brain vasculature responds to neural activity by directing more blood to the active regions. Thus, by detecting changes in blood flow, PET and fMRI reveal the regions of brain that are most active under different circumstances. The advent of imaging techniques has offered neuroscientists the ex- traordinary opportunity of peering into the living, thinking brain. As you can imagine, however, even the most sophisticated brain images are use- less unless you know what you are looking at. Next, let’s take a closer look at how the brain is organized. 179–218_Bear_07_revised_final.indd 190 12/20/14 4:05 AM  CHAPTER 7 THE STRUCTURE OF THE NERVOUS SYSTEM 191 Photon detectors Photon Positron emission Figure A The PET procedure. (Source: Posner and Raichle, 1994, p. 61.) Stimulation Control Difference – = Figure B A PET image. (Source: Posner and Raichle, 1994, p. 65.) S EL F -Q -QUIZ Q UI Z Take a few moments right now and be sure you understand the meaning of these terms: central nervous spinal nerve visceral PNS arachnoid system (CNS) dorsal root autonomic membrane brain ventral root nervous pia mater spinal cord system (ANS) cerebrospinal peripheral cerebrum nervous afferent fluid (CSF) cerebral system (PNS) efferent ventricular hemispheres somatic PNS cranial nerve system cerebellum dorsal root meninges brain stem ganglia dura mater 179–218_Bear_07_revised_final.indd 191 12/20/14 4:05 AM  192 PART ONE FOUNDATIONS UNDE UNDERSTANDING ERSTA ANDING CNS STRU STRUCTURE UCTURE THRO OUGH DEVELOPMENT THROUGH The entire CNS is derived from the walls of a fluid-filled tube that is formed at an early stage in embryonic development. The inside of the tube becomes the adult ventricular system. Thus, by examining how this tube changes during the course of fetal development, we can understand how the brain is organized and how the different parts fit together. This section focuses on development as a way to understand the structural organization of the brain. Chapter 23 will revisit the topic of development to describe how neurons are born, how they find their way to their final locations in the CNS, and how they make the appropriate synaptic con- nections with one another. As you work your way through this section, and through the rest of the book, you will encounter many different names used by anatomists to refer to groups of related neurons and axons. Some common names for describing collections of neurons and axons are given in Tables 7.1 and 7.2. Take a few moments to familiarize yourself with these new terms before continuing. TABLE 7.1 Collections of Neurons Name Na me Desc De Description scri ript ptio ion n an andd Ex Exam Example ampl ple e Gray matter A generic term for a collection of neuronal cell bodies in the CNS. When a freshly dissected brain is cut open, neurons appear gray. Cortex Any collection of neurons that form a thin sheet, usually at the brain’s surface. Cortex is Latin for “bark.” Example: cerebral cortex, the sheet of neurons found just under the surface of the cerebrum. Nucleus A clearly distinguishable mass of neurons, usually deep in the brain (not to be confused with the nucleus of a cell). Nucleus is from the Latin word for “nut.” Example: lateral geniculate nucleus, a cell group in the brain stem that relays information from the eye to the cerebral cortex. Substantia A group of related neurons deep within the brain but usually with less distinct borders than those of nuclei. Example: substantia nigra (from the Latin for “black substance”), a brain stem cell group involved in the control of voluntary movement. Locus A small, well-defined group of cells. Example: locus coeruleus (Latin for “blue spot”), a brain stem cell (plural: loci) group involved in the control of wakefulness and behavioral arousal. Ganglion A collection of neurons in the PNS. Ganglion is from the Greek for “knot.” Example: the dorsal root ganglia, (plural: ganglia) which contain the cell bodies of sensory axons entering the spinal cord via the dorsal roots. Only one cell group in the CNS goes by this name: the basal ganglia, which are structures lying deep within the cerebrum that control movement. TABLE 7.2 Collections of Axons Name Description and Example Nerve A bundle of axons in the PNS. Only one collection of CNS axons is called a nerve: the optic nerve. White matter A generic term for a collection of CNS axons. When a freshly dissected brain is cut open, axons appear white. Tract A collection of CNS axons having a common site of origin and a common destination. Example: corticospinal tract, which originates in the cerebral cortex and ends in the spinal cord. Bundle A collection of axons that run together but do not necessarily have the same origin and destination. Example: medial forebrain bundle, which connects cells scattered within the cerebrum and brain stem. Capsule A collection of axons that connect the cerebrum with the brain stem. Example: internal capsule, which connects the brain stem with the cerebral cortex. Commissure Any collection of axons that connect one side of the brain with the other side. Lemniscus A tract that meanders through the brain like a ribbon. Example: medial lemniscus, which brings touch infor- mation from the spinal cord through the brain stem. 179–218_Bear_07_revised_final.indd 192 12/20/14 4:05 AM  CHAPTER 7 THE STRUCTURE OF THE NERVOUS SYSTEM 193 Anatomy by itself can be pretty dry. It really comes alive only after the functions of different structures are understood. The remainder of this book is devoted to explaining the functional organization of the nervous system. However, we include in this section a preview of some structure- function relationships to provide you with a general sense of how the different parts contribute, individually and collectively, to the function of the CNS. Formation of the Neural Tube The embryo begins as a flat disk with three distinct layers of cells called endoderm, mesoderm, and ectoderm. The endoderm ultimately gives rise to the lining of many of the internal organs (viscera). From the mesoderm arise the bones of the skeleton and the muscles. The nervous system and the skin derive entirely from the ectoderm. Our focus is on changes in the part of the ectoderm that give rise to the nervous system: the neural plate. At this early stage (about 17 days from conception in humans), the brain consists only of a flat sheet of cells (Figure 7.10a). The next event of interest is the formation of a Rostral Caudal Neural Neural Neural Somites Neural Neural Mesoderm Neural groove fold tube crest tube plate Ectoderm (a) (b) (c) (d) Endoderm ▲ FIGURE 7.10 Formation of the neural tube and neural crest. These schematic illustrations follow the early development of the nervous system in the embryo. The drawings above are dorsal views of the embryo; those below are cross sections. (a) The primitive embryonic CNS begins as a thin sheet of ectoderm. (b) The first important step in the develop- ment of the nervous system is the formation of the neural groove. (c) The walls of the groove, called neural folds, come together and fuse, forming the neural tube. (d) The bits of neural ectoderm that are pinched off when the tube rolls up is called the neural crest, from which the PNS will develop. The somites are mesoderm that will give rise to much of the skeletal system and the muscles. 179–218_Bear_07_revised_final.indd 193 12/20/14 4:05 AM  194 PART ONE FOUNDATIONS groove in the neural plate that runs rostral to caudal, called the neural groove (Figure 7.10b). The walls of the groove are called neural folds, which subsequently move together and fuse dorsally, forming the neu- ral tube (Figure 7.10c). The entire central nervous system develops from the walls of the neural tube. As the neural folds come together, some neural ectoderm is pinched off and comes to lie just lateral to the neural tube. This tissue is called the neural crest (Figure 7.10d). All neurons with cell bodies in the peripheral nervous system derive from the neural crest. The neural crest develops in close association with the underlying me- soderm. The mesoderm at this stage in development forms prominent bulges on either side of the neural tube called somites. From these somites, the 33 individual vertebrae of the spinal column and the related skeletal muscles will develop. The nerves that innervate these skeletal muscles are therefore called somatic motor nerves. The process by which the neural plate becomes the neural tube is called neurulation. Neurulation occurs very early in embryonic BOX 7.4 OF SPECIAL INTEREST Nutrition and the Neural Tube N eural tube formation is a crucial event in the development of the nervous system. It occurs early—only 3 weeks after conception—when the mother may be unaware she is preg- nant. Failure of the neural tube to close correctly is a com- mon birth defect, occurring in approximately 1 out of every 500 live births. A recent discovery of enormous public health importance is that many neural tube defects can be traced to a deficiency of the vitamin folic acid (or folate) in the ma- ternal diet during the weeks immediately after conception. It has been estimated that dietary supplementation of folic acid during this period could reduce the incidence of neural tube defects by 90%. Formation of the neural tube is a complex process (Figure A). It depends on a precise sequence of changes in the three-dimensional shape of individual cells as well as on changes in the adhesion of each cell to its neighbors. The timing of neurulation must also be coordinated with simulta- neous changes in non-neural ectoderm and the mesoderm. At the molecular level, successful neurulation depends on specific sequences of gene expression that are controlled, in part, by the position and local chemical environment of the cell. It is not surprising that this process is highly sensi- tive to chemicals, or chemical deficiencies, in the maternal circulation. 0.180 mm The fusion of the neural folds to form the neural tube Figure A occurs first in the middle, then anteriorly and posteriorly Scanning electron micrographs of neurulation. (Figure B). Failure of the anterior neural tube to close results (Source: Smith and Schoenwolf, 1997.) 179–218_Bear_07_revised_final.indd 194 12/20/14 4:05 AM  CHAPTER 7 THE STRUCTURE OF THE NERVOUS SYSTEM 195 development, about 22 days after conception in humans. A common Rostral Prosencephalon birth defect is the failure of appropriate closure of the neural tube. or forebrain Fortunately, recent research suggests that most cases of neural tube defects can be avoided by ensuring proper maternal nutrition during this period (Box 7.4). Mesencephalon or midbrain Three Primary Brain Vesicles The process by which structures become more complex and function- Rhombencephalon ally specialized during development is called differentiation. The first or hindbrain step in the differentiation of the brain is the development, at the ros- Caudal tral end of the neural tube, of three swellings called the primary vesicles ▲ FIGURE 7.11 (Figure 7.11). The entire brain derives from the three primary vesicles of The three primary brain vesicles. The the neural tube. rostral end of the neural tube differenti- The rostral-most vesicle is called the prosencephalon. Pro is Greek for ates to form the three vesicles that will “before”; encephalon is derived from the Greek for “brain.” Thus, the pros- give rise to the entire brain. This view is from above, and the vesicles have been encephalon is also called the forebrain. Behind the prosencephalon lies cut horizontally so that we can see the inside of the neural tube. in anencephaly, a condition characterized by degeneration 22 days 23 days Rostral of the forebrain and skull that is always fatal. Failure of the posterior neural tube to close results in a condition called spina bifida. In its most severe form, spina bifida is charac- terized by the failure of the posterior spinal cord to form from the neural plate (bifida is from the Latin word meaning “cleft in two parts”). Less severe forms are characterized by defects in the meninges and vertebrae overlying the posterior spinal cord. Spina bifida, while usually not fatal, does require exten- sive and costly medical care. Folic acid plays an essential role in a number of meta- Caudal bolic pathways, including the biosynthesis of DNA, which (a) naturally must occur during development as cells divide. Although we do not precisely understand why folic acid de- ficiency increases the incidence of neural tube defects, one can easily imagine how it could alter the complex choreog- raphy of neurulation. Its name is derived from the Latin word for “leaf,” reflecting the fact that folic acid was first isolated from spinach leaves. Besides green leafy vegetables, good dietary sources of folic acid are liver, yeast, eggs, beans, and oranges. Many breakfast cereals are now fortified with folic acid. Nonetheless, the folic acid intake of the average American is only half of what is recommended to prevent birth defects (0.4 mg/day). The U.S. Centers for Disease Normal Anencephaly Spina bifida Control and Prevention recommends that women take mul- (b) tivitamins containing 0.4 mg of folic acid before planning Figure B pregnancy. (a) Neural tube closure. (b) Neural tube defects. 179–218_Bear_07_revised_final.indd 195 12/20/14 4:05 AM  196 PART ONE FOUNDATIONS Telencephalic another vesicle called the mesencephalon, or midbrain. Caudal to this Forebrain vesicles is the third primary vesicle, the rhombencephalon, or hindbrain. The Diencephalon rhombencephalon connects with the caudal neural tube, which gives rise Optic vesicles to the spinal cord. Midbrain Differentiation of the Forebrain Hindbrain The next important developments occur in the forebrain, where second- ary vesicles sprout off on both sides of the prosencephalon. The secondary vesicles are the optic vesicles and the telencephalic vesicles. The central ▲ FIGURE 7.12 structure that remains after the secondary vesicles have sprouted off is The secondary brain vesicles of the called the diencephalon, or “between brain” (Figure 7.12). Thus, the forebrain. The forebrain differentiates forebrain at this stage consists of the two optic vesicles, the two telence- into the paired telencephalic and optic phalic vesicles, and the diencephalon. vesicles, and the diencephalon. The op- tic vesicles develop into the eyes. The optic vesicles grow and invaginate (fold in) to form the optic stalks and the optic cups, which will ultimately become the optic nerves and the two retinas in the adult (Figure 7.13). The important point is that the Cut edge of retina at the back of the eye, and the optic nerve containing the axons optic cup that connect the eye to the diencephalon and midbrain, are part of the Optic brain, not the PNS. stalk Differentiation of the Telencephalon and Diencephalon. The telence- phalic vesicles together form the telencephalon, or “endbrain,” consist- ing of the two cerebral hemispheres. The telencephalon continues to de- velop in four ways. (1) The telencephalic vesicles grow posteriorly so that they lie over and lateral to the diencephalon (Figure 7.14a). (2) Another Cut edge of wall pair of vesicles sprout off the ventral surfaces of the cerebral hemispheres, of diencephalon giving rise to the olfactory bulbs and related structures that partici- pate in the sense of smell (Figure 7.14b). (3) The cells of the walls of the ▲ FIGURE 7.13 Early development of the eye. The op- telencephalon divide and differentiate into various structures. (4) White tic vesicle differentiates into the optic matter systems develop, carrying axons to and from the neurons of the stalk and the optic cup. The optic stalk telencephalon. will become the optic nerve, and the op- tic cup will become the retina. Telencephalon Dorsal Cerebral (2 cerebral hemispheres) hemispheres Caudal Rostral Rostral Ventral Diencephalon Midbrain Hindbrain Diencephalon Optic cups Olfactory Caudal bulbs (a) Differentiation (b) ▲ FIGURE 7.14 Differentiation of the telencephalon. (a) As development proceeds, the cerebral hemispheres swell and grow posteriorly and laterally to envelop the diencephalon. (b) The olfactory bulbs sprout off the ventral surfaces of each telencephalic vesicle. 179–218_Bear_07_revised_final.indd 196 12/20/14 4:05 AM  CHAPTER 7 THE STRUCTURE OF THE NERVOUS SYSTEM 197 Figure 7.15 shows a coronal section through the primitive mammalian forebrain, to illustrate how the different parts of the telencephalon and diencephalon differentiate and fit together. Notice that the two cerebral hemispheres lie above and on either side of the diencephalon, and that the ventral–medial surfaces of the hemispheres have fused with the lat- eral surfaces of the diencephalon (Figure 7.15a). The fluid-filled spaces within the cerebral hemispheres are called the lateral ventricles, and the space at the center of the diencephalon is called the third ventricle (Figure 7.15b). The paired lateral ventricles are a key landmark in the adult brain: Whenever you see paired fluid- filled ventricles in a brain section, you know that the tissue surrounding them is in the telencephalon. The elongated, slit-like appearance of the third ventricle in cross section is also a useful feature for identifying the diencephalon. Notice in Figure 7.15 that the walls of the telencephalic vesicles ap- pear swollen due to the proliferation of neurons. These neurons form two different types of gray matter in the telencephalon: the cerebral cortex and the basal telencephalon. Likewise, the diencephalon dif- ferentiates into two structures: the thalamus and the hypothalamus (Figure 7.15c). The thalamus, nestled deep inside the forebrain, gets its name from the Greek word for “inner chamber.” The neurons of the developing forebrain extend axons to communicate with other parts of the nervous system. These axons bundle together to form three major white matter systems: the cortical white matter, the corpus callosum, and the internal capsule (Figure 7.15d). The cortical white matter contains all the axons that run to and from the neurons in the cerebral cortex. The corpus callosum is continuous with the cortical white matter and forms an axonal bridge that links cortical neurons of the two cerebral hemispheres. The cortical white matter is also continu- Telencephalon Cerebral cortex Thalamus Hypothalamus Diencephalon Basal telencephalon (a) Main divisions (c) Gray matter structures Lateral ventricles Corpus callosum Cortical white Third ventricle matter Internal capsule (b) Ventricles (d) White matter structures ▲ FIGURE 7.15 Structural features of the forebrain. (a) A coronal section through the primitive forebrain, showing the two main divisions: the telencephalon and the diencepha- lon. (b) Ventricles of the forebrain. (c) Gray matter of the forebrain. (d) White mat- ter structures of the forebrain. 179–218_Bear_07_revised_final.indd 197 12/20/14 4:05 AM  198 PART ONE FOUNDATIONS Cerebral ous with the internal capsule, which links the cortex with the brain cortex stem, particularly the thalamus. Forebrain Structure-Function Relationships. The forebrain is the seat of perceptions, conscious awareness, cognition, and voluntary action. All this depends on extensive interconnections with the sensory and motor Thalamus neurons of the brain stem and spinal cord. Arguably the most important structure in the forebrain is the cerebral cortex. As we will see later in this chapter, the cortex is the brain struc- ture that has expanded the most over the course of human evolution. Cortical neurons receive sensory information, form perceptions of the out- side world, and command voluntary movements. Neurons in the olfactory bulbs receive information from cells that sense chemicals in the nose (odors), and relay this information caudally to a part of the cerebral cortex for further analysis. Information from the eyes, ears, and skin is also brought to the cerebral cortex for analysis. Eye Ear Skin However, each of the sensory pathways serving vision, audition (hear- ▲ FIGURE 7.16 ing), and somatic sensation relays (i.e., synapses upon neurons) in the The thalamus: gateway to the cerebral cortex. The sensory pathways from the thalamus en route to the cortex. Thus, the thalamus is often referred to eye, ear, and skin all relay in the thala- as the gateway to the cerebral cortex (Figure 7.16). mus before terminating in the cerebral Thalamic neurons send axons to the cortex via the internal capsule. cortex. The arrows indicate the direction As a general rule, the axons of each internal capsule carry information of information flow. to the cortex about the contralateral side of the body. Therefore, if a thumbtack entered the right foot, it would be relayed to the left cortex by the left thalamus via axons in the left internal capsule. But how does the right foot know what the left foot is doing? One important way is by communication between the hemispheres via the axons in the corpus callosum. Cortical neurons also send axons through the internal capsule, back to the brain stem. Some cortical axons course all the way to the spinal cord, forming the corticospinal tract. This is one important way cortex can command voluntary movement. Another way is by communicating with neurons in the basal ganglia, a collection of cells in the basal tel- encephalon. The term basal is used to describe structures deep in the brain, and the basal ganglia lie deep within the cerebrum. The func- tions of the basal ganglia are poorly understood, but it is known that damage to these structures disrupts the ability to initiate voluntary movement. Other structures, contributing to other brain functions, are also present in the basal telencephalon. For example, in Chapter 18, we’ll discuss a structure called the amygdala that is involved in fear and emotion. Although the hypothalamus lies just under the thalamus, function- ally it is more closely related to certain telencephalic structures like the amygdala. The hypothalamus performs many primitive functions and therefore has not changed much over the course of mammalian evolu- tion. “Primitive” does not mean unimportant or uninteresting, however. The hypothalamus controls the visceral (autonomic) nervous system, which regulates bodily functions in response to the needs of the organ-