The Structure of the Nervous System

The Structure of the Nervous System

GROSS ORGANIZATION OF THE MAMMALIAN NERVOUS SYSTEM

BOX 7.4 OF SPECIAL INTEREST: Nutrition and the Neural Tube

Differentiation of the Telencephalon and Diencephalon

Neocortical Evolution and Structure-Function Relationships

BOX 7.5 PATH OF DISCOVERY: Connecting with the Connectome, by Sebastian Seung

APPENDIX: AN ILLUSTRATED GUIDE TO HUMAN NEUROANATOMY

In previous chapters, we saw how individual neurons function and communicate. Now we are ready to assemble them into a nervous system that sees, hears, feels, moves, remembers, and dreams. Just as an understanding of neuronal structure is necessary for understanding neuronal 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 specializations of the human brain become clear.


FIGURE 7.1 Mammalian brains. Despite differences in complexity, the brains of all these species have many features in common. The brains have been drawn to appear approximately the same size; their relative sizes are shown in the inset on the left.

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.

GROSS ORGANIZATION OF THE MAMMALIAN NERVOUS SYSTEM

The nervous system of all mammals has two divisions: the central nervous 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 examining the structure of the brain. But first, we need to review some anatomical terminology.

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 direction, 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”). Thus, the rat spinal cord runs anterior to posterior. The top side of the spinal cord is the dorsal side, and the bottom side is the ventral side.


FIGURE 7.2 Basic anatomical references in the nervous system of a rat. (a) Side view. (b) Top view. Description

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 anatomical 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 addition, 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 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 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.


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.

Take a few moments right now and be sure you understand the meaning of these terms:

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 cerebellum, and the brain stem (Figure 7.4a).


FIGURE 7.4 The brain of a rat. (a) Side (lateral) view. (b) Top (dorsal) view. (c) Midsagittal view. Description

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 neurons as both cerebral hemispheres combined. The cerebellum is primarily a movement control center that has extensive connections with the cerebrum 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 cerebellum, 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 important 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 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 carrying information away from the spinal cord—for example, to the muscles that jerk your foot away in response to the pain of the thumbtack.


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.

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, derive 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 dorsal roots. The cell bodies of these neurons lie outside the spinal cord in 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, vegetative, 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 regulating 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 system. 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.

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 CNS, that part of the nervous system encased in the skull and vertebral 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).


FIGURE 7.6 The meninges. (a) The skull has been removed to show the tough outer meningeal 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 outermost covering is the dura mater, from the Latin words meaning “hard mother,” an accurate description of the dura’s leatherlike consistency. 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.

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 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.

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 apertures, 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).


FIGURE 7.7 The ventricular system in a rat brain. CSF is produced in the ventricles of the paired cerebral hemispheres and flows through a series of central ventricles at the core of the brain stem. CSF escapes into the subarachnoid space via small apertures near the base of the cerebellum. In the subarachnoid space, CSF is absorbed into the blood.

If the flow of CSF from the choroid plexus through the ventricular 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 “water head.”

Occasionally, babies are born with hydrocephalus. 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 situation 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 inserting a tube into the swollen ventricle and draining off the excess fluid (Figure A).


We will return to fill in some details about the ventricular system in a moment. As we will see, understanding the organization of the ventricular system holds the key to understanding how the mammalian brain is organized.

For centuries, anatomists have investigated the internal structure of the brain by removing it from the skull, sectioning it in various planes, staining the sections, and examining the stained sections. Much has been learned by this approach, but there are some limitations. Among these are the challenges of seeing how parts deep in the brain fit together in 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 lipids 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 transparent 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 transparent brain illuminated to evoke fluorescence from neurons that express green fluorescent protein. (Source: Courtesy of Dr. Kwanghun Chung, Massachusetts Institute of Technology. Adapted from Chung and Deisseroth. 2013, Figure 2.)

Of course, a clarified brain is still a dead brain. This, to say the least, limits the usefulness of such anatomical methods for diagnosing neurological 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 developed 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 reconstruction 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 advantages 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 magnetic 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 powerful 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.

Magnetic resonance imaging (MRI) is a general technique that can be used for determining the amount of certain atoms at different locations in the body. It has become an important tool in neuroscience because it can be used noninvasively to obtain a detailed picture of the nervous system, particularly the brain.

In the most common form of MRI, the hydrogen atoms are quantified—for instance, those located in water or fat in the brain. An important fact of physics is that when a hydrogen atom is put in a magnetic field, its nucleus (which consists of a single proton) can exist in either of two states: a high-energy state or a low-energy state. Because hydrogen atoms are abundant in the brain, there are many protons in each state.

The key to MRI is making the protons jump from one state to the other. Energy is added to the protons by passing an electromagnetic wave (i.e., a radio signal) through the head while it is positioned between the poles of a large magnet. When the radio signal is set at just the right frequency, the protons in the low-energy state will absorb energy from the signal and hop to the high-energy state. The frequency at which the protons absorb energy is called the resonant frequency (hence the name magnetic resonance). When the radio signal is turned off, some of the protons fall back down to the low-energy state, thereby emitting a radio signal of their own at a particular frequency. This signal can be picked up by a radio receiver. The stronger the signal, the more hydrogen atoms between the poles of the magnet.

If we used the procedure discussed earlier, we would simply get a measurement of the total amount of hydrogen in the head. However, it is possible to measure hydrogen amounts at a fine spatial scale by taking advantage of the fact that the frequency at which protons emit energy is proportional to the size of the magnetic field. In the MRI machines used in hospitals, the magnetic fields vary from one side of the magnet to the other. This gives a spatial code to the radio waves emitted by the protons: High-frequency signals come from hydrogen atoms near the strong side of the magnet, and low-frequency signals come from the weak side of the magnet.

The last step in the MRI process is to orient the gradient of the magnet at many different angles relative to the head and measure the amount of hydrogen. It takes about 15 minutes to make all the measurements for a typical brain scan. A sophisticated computer program is then used to make a single image from the measurements, resulting in a picture of the distribution of hydrogen atoms in the head.

Figure A is an MRI image of a lateral view of the brain in a living human. In Figure B, another MRI image, a slice has been made in the brain. Notice how clearly you can see the white and gray matter. This differentiation makes it possible to see the effects of demyelinating diseases on white matter in the brain. MRI images also reveal lesions in the brain because tumors and inflammation generally increase the amount of extracellular water.



Another application of MRI, called diffusion tensor imaging (DTI), enables visualization of large bundles of axons in the brain. By comparing the position of the hydrogen atoms in water molecules at discrete time intervals, the diffusion of water in the brain can be measured. Water diffuses much more readily alongside axon membranes than across them, and this difference can be used to detect axon bundles that connect different regions of the brain (Figure 7.9).


FIGURE 7.9 Diffusion tensor imaging of the human brain. Displayed is a computer reconstruction of axon bundles in a living human brain viewed from the side. Anterior is to the left. The bundles are pseudocolored based on the direction of water diffusion. (Source: Courtesy of Dr. Satrajit Ghosh, Massachusetts Institute of Technology.)

Functional Brain Imaging. CT and MRI are extremely valuable for detecting structural changes in the living brain, such as brain swelling after a head injury and brain tumors. Nonetheless, much of what goes on in the brain—healthy or diseased—is chemical and electrical in nature and not observable by simple inspection of the brain’s anatomy. Amazingly, however, even these secrets are beginning to yield to the newest imaging techniques.

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 glucose 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.

Until recently, “mind reading” has been beyond the reach of science. However, with the introduction of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), it is now possible to observe and measure changes in brain activity associated with the planning and execution of specific tasks.

PET imaging was developed in the 1970s by two groups of physicists, one at Washington University led by M. M. Ter-Pogossian and M. E. Phelps, and a second at UCLA led by Z. H. Cho. The basic procedure is very simple. A radioactive solution containing atoms that emit positrons (positively charged electrons) is introduced into the bloodstream. Positrons, emitted wherever the blood goes, interact with electrons to produce photons of electromagnetic radiation. The locations of the positron-emitting atoms are found by detectors that pick up the photons.

One powerful application of PET is the measurement of metabolic activity in the brain. In a technique developed by Louis Sokoloff and his colleagues at the National Institute of Mental Health, a positron-emitting isotope of fluorine or oxygen is attached to 2-deoxyglucose (2-DG). This radioactive 2-DG is injected into the bloodstream and travels to the brain. Metabolically active neurons, which normally use glucose, also take up the 2-DG. The 2-DG is phosphorylated by enzymes inside the neuron, and this modification prevents the 2-DG from leaving. Thus, the amount of radioactive 2-DG accumulated in a neuron and the number of positron emissions indicate the level of neuronal metabolic activity.

In a typical PET application, a person’s head is placed in an apparatus surrounded by detectors (Figure A). Using computer algorithms, the photons (resulting from positron emissions) reaching each of the detectors are recorded. With this information, levels of activity for populations of neurons at various sites in the brain can be calculated. Compiling these measurements produces an image of the brain activity pattern. The researcher monitors brain activity while the subject performs a task, such as moving a finger or reading aloud. Different tasks “light up” different brain areas. In order to obtain a picture of the activity induced by a particular behavioral or thought task, a subtraction technique is used. Even in the absence of any sensory stimulation, the PET image will contain a great deal of brain activity. To create an image of the brain activity resulting from a specific task, such as a person looking at a picture, this background activity is subtracted out (Figure B).


Figure A The PET procedure. (Source: Posner and Raichle, 1994, p. 61.)


Figure B A PET image. (Source: Posner and Raichle, 1994, p. 65.)

Although PET imaging has proven to be a valuable technique, it has significant limitations. Because the spatial resolution is only 5–10 mm3, the images show the activity of many thousands of cells. Also, a single PET brain scan may take one to several minutes to obtain. This, along with concerns about radiation exposure, limits the number of scans that can be obtained from one person in a reasonable time period. Thus, the work of S. Ogawa at Bell Labs, showing that MRI techniques could be used to measure local changes in blood oxygen levels that result from brain activity, was an important advance.

The fMRI method takes advantage of the fact that oxyhemoglobin (the oxygenated from of hemoglobin in the blood) has a magnetic resonance different from that of deoxyhemoglobin (hemoglobin that has donated its oxygen). More active regions of the brain receive more blood, and this blood donates more of its oxygen. Functional MRI detects the locations of increased neural activity by measuring the ratio of oxyhemoglobin to deoxyhemoglobin. It has emerged as the method of choice for functional brain imaging because the scans can be made rapidly (50 msec), they have good spatial resolution (3 mm3), and they are completely noninvasive.

The advent of imaging techniques has offered neuroscientists the extraordinary opportunity of peering into the living, thinking brain. As you can imagine, however, even the most sophisticated brain images are useless unless you know what you are looking at. Next, let’s take a closer look at how the brain is organized.

Take a few moments right now and be sure you understand the meaning of these terms:

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 connections 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.

A generic term for a collection of neuronal cell bodies in the CNS. When a freshly dissected brain is cut open, neurons appear gray.

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.

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.

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.

A small, well-defined group of cells. Example: locus coeruleus (Latin for “blue spot”), a brain stem cell group involved in the control of wakefulness and behavioral arousal.

A collection of neurons in the PNS. Ganglion is from the Greek for “knot.” Example: the dorsal root 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.

A bundle of axons in the PNS. Only one collection of CNS axons is called a nerve: the optic nerve.

A generic term for a collection of CNS axons. When a freshly dissected brain is cut open, axons appear white.

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.

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.

A collection of axons that connect the cerebrum with the brain stem. Example: internal capsule, which connects the brain stem with the cerebral cortex.

Any collection of axons that connect one side of the brain with the other side.

A tract that meanders through the brain like a ribbon. Example: medial lemniscus, which brings touch information from the spinal cord through the brain stem.

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.

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 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 neural 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.


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 development 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. Description

The neural crest develops in close association with the underlying mesoderm. 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 development, about 22 days after conception in humans. A common birth defect is the failure of appropriate closure of the neural tube. 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).

Neural 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 pregnant. Failure of the neural tube to close correctly is a common 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 maternal 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 simultaneous 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 sensitive to chemicals, or chemical deficiencies, in the maternal circulation.


Figure A Scanning electron micrographs of neurulation. (Source: Smith and Schoenwolf, 1997.)

The fusion of the neural folds to form the neural tube occurs first in the middle, then anteriorly and posteriorly (Figure B). Failure of the anterior neural tube to close results in anencephaly, a condition characterized by degeneration 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 characterized 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 extensive and costly medical care.


Figure B (a) Neural tube closure. (b) Neural tube defects.

Folic acid plays an essential role in a number of metabolic pathways, including the biosynthesis of DNA, which naturally must occur during development as cells divide. Although we do not precisely understand why folic acid deficiency increases the incidence of neural tube defects, one can easily imagine how it could alter the complex choreography 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 Control and Prevention recommends that women take multivitamins containing 0.4 mg of folic acid before planning pregnancy.

The process by which structures become more complex and functionally specialized during development is called differentiation. The first step in the differentiation of the brain is the development, at the rostral end of the neural tube, of three swellings called the primary vesicles (Figure 7.11). The entire brain derives from the three primary vesicles of the neural tube.


FIGURE 7.11 The three primary brain vesicles. The rostral end of the neural tube differentiates to form the three vesicles that will give rise to the entire brain. This view is from above, and the vesicles have been cut horizontally so that we can see the inside of the neural tube.

The rostral-most vesicle is called the prosencephalon. Pro is Greek for “before”; encephalon is derived from the Greek for “brain.” Thus, the prosencephalon is also called the forebrain. Behind the prosencephalon lies another vesicle called the mesencephalon, or midbrain. Caudal to this is the third primary vesicle, the rhombencephalon, or hindbrain. The rhombencephalon connects with the caudal neural tube, which gives rise to the spinal cord.

The next important developments occur in the forebrain, where secondary vesicles sprout off on both sides of the prosencephalon. The secondary vesicles are the optic vesicles and the telencephalic vesicles. The central structure that remains after the secondary vesicles have sprouted off is called the diencephalon, or “between brain” (Figure 7.12). Thus, the forebrain at this stage consists of the two optic vesicles, the two telencephalic vesicles, and the diencephalon.


FIGURE 7.12 The secondary brain vesicles of the forebrain. The forebrain differentiates into the paired telencephalic and optic vesicles, and the diencephalon. The optic 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 retina at the back of the eye, and the optic nerve containing the axons that connect the eye to the diencephalon and midbrain, are part of the brain, not the PNS.


FIGURE 7.13 Early development of the eye. The optic vesicle differentiates into the optic stalk and the optic cup. The optic stalk will become the optic nerve, and the optic cup will become the retina.

Differentiation of the Telencephalon and Diencephalon. The telencephalic vesicles together form the telencephalon, or “endbrain,” consisting of the two cerebral hemispheres. The telencephalon continues to develop in four ways. (1) The telencephalic vesicles grow posteriorly so that they lie over and lateral to the diencephalon (Figure 7.14a). (2) Another pair of vesicles sprout off the ventral surfaces of the cerebral hemispheres, giving rise to the olfactory bulbs and related structures that participate in the sense of smell (Figure 7.14b). (3) The cells of the walls of the telencephalon divide and differentiate into various structures. (4) White matter systems develop, carrying axons to and from the neurons of the telencephalon.


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.

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 lateral surfaces of the diencephalon (Figure 7.15a).


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 diencephalon. (b) Ventricles of the forebrain. (c) Gray matter of the forebrain. (d) White matter structures of the forebrain. Description

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 appear 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 differentiates 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 continuous with the internal capsule, which links the cortex with the brain 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 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 structure that has expanded the most over the course of human evolution. Cortical neurons receive sensory information, form perceptions of the outside 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. However, each of the sensory pathways serving vision, audition (hearing), and somatic sensation relays (i.e., synapses upon neurons) in the thalamus en route to the cortex. Thus, the thalamus is often referred to as the gateway to the cerebral cortex (Figure 7.16).


FIGURE 7.16 The thalamus: gateway to the cerebral cortex. The sensory pathways from the eye, ear, and skin all relay in the thalamus before terminating in the cerebral cortex. The arrows indicate the direction of information flow.

Thalamic neurons send axons to the cortex via the internal capsule. As a general rule, the axons of each internal capsule carry information 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 telencephalon. The term basal is used to describe structures deep in the brain, and the basal ganglia lie deep within the cerebrum. The functions 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, functionally 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 evolution. “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 organism. For example, when you are faced with a threatening situation, the hypothalamus orchestrates the body’s visceral fight-or-flight response. Hypothalamic commands to the ANS will lead to (among other things) an increase in the heart rate, increased blood flow to the muscles for escape, and even the standing of your hair on end. Conversely, when you’re relaxing after Sunday brunch, the hypothalamus ensures that the brain is well nourished via commands to the ANS, which will increase peristalsis (movement of material through the gastrointestinal tract) and redirect blood to your digestive system. The hypothalamus also plays a key role in motivating animals to find food, drink, and sex in response to their needs. Aside from its connections to the ANS, the hypothalamus also directs bodily responses via connections with the pituitary gland located below the diencephalon. This gland communicates with many parts of the body by releasing hormones into the bloodstream.

Listed below are derivatives of the forebrain that we have discussed. Be sure you know what each of these terms means.

Unlike the forebrain, the midbrain differentiates relatively little during subsequent brain development (Figure 7.17). The dorsal surface of the mesencephalic vesicle becomes a structure called the tectum (Latin for “roof”). The floor of the midbrain becomes the tegmentum. The CSF-filled space in between constricts into a narrow channel called the cerebral aqueduct. The aqueduct connects rostrally with the third ventricle of the diencephalon. Because it is small and circular in cross section, the cerebral aqueduct is a good landmark for identifying the midbrain.


FIGURE 7.17 Differentiation of the midbrain. The midbrain differentiates into the tectum and the tegmentum. The CSF-filled space at the core of the midbrain is the cerebral aqueduct. (Drawings are not to scale.)

Midbrain Structure-Function Relationships. For such a seemingly simple structure, the functions of the midbrain are remarkably diverse. Besides serving as a conduit for information passing from the spinal cord to the forebrain and vice versa, the midbrain contains neurons that contribute to sensory systems, the control of movement, and several other functions.

The midbrain contains axons descending from the cerebral cortex to the brain stem and the spinal cord. For example, the corticospinal tract courses through the midbrain en route to the spinal cord. Damage to this tract in the midbrain on one side produces a loss of voluntary control of movement on the opposite side of the body.

The tectum differentiates into two structures: the superior colliculus and the inferior colliculus. The superior colliculus receives direct input from the eye, so it is also called the optic tectum. One function of the optic tectum is to control eye movements, which it does via synaptic connections with the motor neurons that innervate the eye muscles. Some of the axons that supply the eye muscles originate in the midbrain, bundling together to form cranial nerves III and IV.

The inferior colliculus also receives sensory information but from the ear instead of the eye. The inferior colliculus serves as an important relay station for auditory information en route to the thalamus.

The tegmentum is one of the most colorful regions of the brain because it contains both the substantia nigra (the black substance) and the red nucleus. These two cell groups are involved in the control of voluntary movement. Other cell groups scattered in the midbrain have axons that project widely throughout much of the CNS and function to regulate consciousness, mood, pleasure, and pain.

The hindbrain differentiates into three important structures: the cerebellum, the pons, and the medulla oblongata—also simply called the medulla. The cerebellum and pons develop from the rostral half of the hindbrain (called the metencephalon); the medulla develops from the caudal half (called the myelencephalon). The CSF-filled tube becomes the fourth ventricle, which is continuous with the cerebral aqueduct of the midbrain.

At the three-vesicle stage, the rostral hindbrain in cross section is a simple tube. In subsequent weeks, the tissue along the dorsal–lateral wall of the tube, called the rhombic lip, grows dorsally and medially until it fuses with its twin on the other side. The resulting flap of brain tissue grows into the cerebellum. The ventral wall of the tube differentiates and swells to form the pons (Figure 7.18).


FIGURE 7.18 Differentiation of the rostral hindbrain. The rostral hindbrain differentiates into the cerebellum and pons. The cerebellum is formed by the growth and fusion of the rhombic lips. The CSF-filled space at the core of the hindbrain is the fourth ventricle. (Drawings are not to scale.)

Less dramatic changes occur during the differentiation of the caudal half of the hindbrain into the medulla. The ventral and lateral walls of this region swell, leaving the roof covered only with a thin layer of non-neuronal ependymal cells (Figure 7.19). Along the ventral surface of each side of the medulla runs a major white matter system. Cut in cross section, these bundles of axons appear somewhat triangular in shape, explaining why they are called the medullary pyramids.


FIGURE 7.19 Differentiation of the caudal hindbrain. The caudal hindbrain differentiates into the medulla. The medullary pyramids are bundles of axons coursing caudally toward the spinal cord. The CSF-filled space at the core of the medulla is the fourth ventricle. (Drawings are not to scale.)

Hindbrain Structure-Function Relationships. Like the midbrain, the hindbrain is an important conduit for information passing from the forebrain to the spinal cord, and vice versa. In addition, neurons of the hindbrain contribute to the processing of sensory information, the control of voluntary movement, and regulation of the autonomic nervous system.

The cerebellum, the “little brain,” is an important movement control center. It receives massive axonal inputs from the spinal cord and the pons. The spinal cord inputs provide information about the body’s position in space. The inputs from the pons relay information from the cerebral cortex, specifying the goals of intended movements. The cerebellum compares these types of information and calculates the sequences of muscle contractions that are required to achieve the movement goals. Damage to the cerebellum results in uncoordinated and inaccurate movements.

Of the descending axons passing through the midbrain, over 90%—about 20 million axons in the human—synapse on neurons in the pons. The pontine cells relay all this information to the cerebellum on the opposite site. Thus, the pons serves as a massive switchboard connecting the cerebral cortex to the cerebellum. (The word pons is from the Latin word for “bridge.”) The pons bulges out from the ventral surface of the brain stem to accommodate all this circuitry.

The axons that do not terminate in the pons continue caudally and enter the medullary pyramids. Most of these axons originate in the cerebral cortex and are part of the corticospinal tract. Thus, “pyramidal tract” is often used as a synonym for corticospinal tract. Near where the medulla joins with the spinal cord, each pyramidal tract crosses from one side of the midline to the other. A crossing of axons from one side to the other is known as a decussation, and this one is called the pyramidal decussation. The crossing of axons in the medulla explains why the cortex of one side of the brain controls movements on the opposite side of the body (Figure 7.20).


FIGURE 7.20 The pyramidal decussation. The corticospinal tract crosses from one side to the other in the medulla.

In addition to the white matter systems passing through, the medulla contains neurons that perform many different sensory and motor functions. For example, the axons of the auditory nerves, bringing auditory information from the ears, synapse on cells in the cochlear nuclei of the medulla. The cochlear nuclei project axons to a number of different structures, including the tectum of the midbrain (the inferior colliculus, discussed above). Damage to the cochlear nuclei leads to deafness.

Other sensory functions of the medulla include touch and taste. The medulla contains neurons that relay somatic sensory information from the spinal cord to the thalamus. Destruction of the cells leads to anesthesia (loss of feeling). Other neurons relay gustatory (taste) information from the tongue to the thalamus. And among the motor neurons in the medulla are cells that control the tongue muscles via cranial nerve XII. (So think of the medulla next time you stick out your tongue!)

Listed below are derivatives of the midbrain and hindbrain that we have discussed. Be sure you know what each of these terms means.

As shown in Figure 7.21, the transformation of the caudal neural tube into the spinal cord is straightforward compared to the differentiation of the brain. With the expansion of the tissue in the walls, the cavity of the tube constricts to form the tiny CSF-filled spinal canal.


FIGURE 7.21 Differentiation of the spinal cord. The butterfly-shaped core of the spinal cord is gray matter, divisible into dorsal and ventral horns, and an intermediate zone. Surrounding the gray matter are white matter columns running rostrocaudally, up and down the cord. The narrow CSF-filled channel is the spinal canal. (Drawings are not to scale.) Description

Cut in cross section, the gray matter of the spinal cord (where the neurons are) has the appearance of a butterfly. The upper part of the butterfly’s wing is the dorsal horn, and the lower part is the ventral horn. The gray matter between the dorsal and ventral horns is called the intermediate zone. Everything else is white matter, consisting of columns of axons that run up and down the spinal cord. Thus, the bundles of axons running along the dorsal surface of the cord are called the dorsal columns, the bundles of axons lateral to the spinal gray matter on each side are called the lateral columns, and the bundles on the ventral surface are called the ventral columns.

Spinal Cord Structure-Function Relationships. As a general rule, dorsal horn cells receive sensory inputs from the dorsal root fibers, ventral horn cells project axons into the ventral roots that innervate muscles, and intermediate zone cells are interneurons that shape motor outputs in response to sensory inputs and descending commands from the brain.

The large dorsal column contains axons that carry somatic sensory (touch) information up the spinal cord toward the brain. It’s like a superhighway that speeds information from the ipsilateral side of the body up to nuclei in the medulla. The postsynaptic neurons in the medulla give rise to axons that decussate and ascend to the thalamus on the contralateral side. This crossing of axons in the medulla explains why touching the left side of the body is sensed by the right side of the brain.

The lateral column contains the axons of the descending corticospinal tract, which also cross from one side to the other in the medulla. These axons innervate the neurons of the intermediate zone and ventral horn and communicate the signals that control voluntary movement.

There are at least a half-dozen tracts that run in the columns of each side of the spinal cord. Most are one-way and bring information to or from the brain. Thus, the spinal cord is the major conduit of information from the skin, joints, and muscles to the brain, and vice versa. However, the spinal cord is also much more than that. The neurons of the spinal gray matter begin the analysis of sensory information, play a critical role in coordinating movements, and orchestrate simple reflexes (such as jerking away your foot from a thumbtack).

We have discussed the development of different parts of the CNS: the telencephalon, diencephalon, midbrain, hindbrain, and spinal cord. Now let’s put all the individual pieces together to make a whole central nervous system.

Figure 7.22 is a highly schematic illustration that captures the basic organizational plan of the CNS of all mammals, including humans. The paired hemispheres of the telencephalon surround the lateral ventricles. Dorsal to the lateral ventricles, at the surface of the brain, lies the cortex. Ventral and lateral to the lateral ventricles lies the basal telencephalon. The lateral ventricles are continuous with the third ventricle of the diencephalon. Surrounding this ventricle are the thalamus and the hypothalamus. The third ventricle is continuous with the cerebral aqueduct. Dorsal to the aqueduct is the tectum. Ventral to the aqueduct is the midbrain tegmentum. The aqueduct connects with the fourth ventricle that lies at the core of the hindbrain. Dorsal to the fourth ventricle sprouts the cerebellum. Ventral to the fourth ventricle lie the pons and the medulla.


FIGURE 7.22 The “brainship Enterprise.” (a) The basic plan of the mammalian brain, with the major subdivisions indicated. (b) Major structures within each division of the brain. Note that the telencephalon consists of two hemispheres, although only one is illustrated. (c) The ventricular system. Description

You should see by now that finding your way around the brain is easy if you can identify which parts of the ventricular system are in the neighborhood (Table 7.3). Even in the complicated human brain, the ventricular system holds the key to understanding brain structure.

So far, we’ve explored the basic plan of the CNS as it applies to all mammals. Figure 7.23 compares the brains of the rat and the human. You can see immediately that there are indeed many similarities but also some obvious differences.


FIGURE 7.23 The rat brain and human brain compared. (a) Dorsal view. (b) Midsagittal view. (c) Lateral view. (Brains are not drawn to the same scale.) Description

Let’s start by reviewing the similarities. The dorsal view of both brains reveals the paired hemispheres of the telencephalon (Figure 7.23a). A midsagittal view of the two brains shows the telencephalon extending rostrally from the diencephalon (Figure 7.23b). The diencephalon surrounds the third ventricle, the midbrain surrounds the cerebral aqueduct, and the cerebellum, pons, and medulla surround the fourth ventricle. Notice how the pons swells below the cerebellum, and how structurally elaborate the cerebellum is.

Now let’s consider some of the structural differences between the rat and human brains. Figure 7.23a reveals a striking one: the many convolutions on the surface of the human cerebrum. The grooves in the surface of the cerebrum are called sulci (singular: sulcus), and the bumps are called gyri (singular: gyrus). Remember, the thin sheet of neurons that lies just under the surface of the cerebrum is the cerebral cortex. Sulci and gyri result from the tremendous expansion of the surface area of the cerebral cortex during human fetal development. The adult human cortex, measuring about 1100 cm2, must fold and wrinkle to fit within the confines of the skull. This increase in cortical surface area is one of the “distortions” of the human brain. Clinical and experimental evidence indicates that the cortex is the seat of uniquely human reasoning and cognition. Without cerebral cortex, a person would be blind, deaf, dumb, and unable to initiate voluntary movement. We will take a closer look at the structure of the cerebral cortex in a moment.

The side views of the rat and human brains in Figure 7.23c reveal further differences in the forebrain. One is the small size of the olfactory bulb in the human relative to the rat. On the other hand, notice again the growth of the cerebral hemisphere in the human. See how the cerebral hemisphere of the human brain arcs posteriorly, ventrolaterally, and then anteriorly to resemble a ram’s horn. The tip of the “horn” lies right under the temporal bone (temple) of the skull, so this portion of the brain is called the temporal lobe (Figure 7.24). Three other lobes (named after skull bones) also describe the parts of human cerebrum. The portion of the cerebrum lying just under the frontal bone of the forehead is called the frontal lobe. The deep central sulcus marks the posterior border of the frontal lobe, caudal to which lies the parietal lobe, under the parietal bone. Caudal to that, at the back of the cerebrum under the occipital bone, lies the occipital lobe.


It is important to realize that, despite the disproportionate growth of the cerebrum, the human brain still follows the basic mammalian brain plan laid out during embryonic development. Again, the ventricles are key. Although the ventricular system is distorted, particularly by the growth of the temporal lobes, the relationships that relate the brain to the different ventricles still hold (Figure 7.25).


FIGURE 7.25 The human ventricular system. Although the ventricles are distorted by the growth of the brain, the basic relationships of the ventricles to the surrounding brain are the same as those illustrated in Figure 7.22c.

Considering its prominence in the human brain, the cerebral cortex deserves further description. As we will see repeatedly in subsequent chapters, the systems in the brain that govern the processing of sensations, perceptions, voluntary movement, learning, speech, and cognition all converge in this remarkable organ.

Cerebral cortex in the brain of all vertebrate animals has several common features, as shown in Figure 7.26. First, the cell bodies of cortical neurons are always arranged in layers, or sheets, that usually lie parallel to the surface of the brain. Second, the layer of neurons closest to the surface (the most superficial cell layer) is separated from the pia mater by a zone that lacks neurons; it is called the molecular layer, or simply layer I. Third, at least one cell layer contains pyramidal cells that emit large dendrites, called apical dendrites, that extend up to layer I, where they form multiple branches. Thus, we can say that the cerebral cortex has a characteristic cytoarchitecture that distinguishes it, for example, from the nuclei of the basal telencephalon or the thalamus.


FIGURE 7.26 General features of the cerebral cortex. On the left is the structure of cortex in an alligator; on the right, a rat. In both species, the cortex lies just under the pia mater of the cerebral hemisphere, contains a molecular layer, and has pyramidal cells arranged in layers. Description

Figure 7.27 shows a Nissl-stained coronal section through the caudal telencephalon of a rat brain. You don’t need to be Cajal to see that different types of cortex can also be discerned based on cytoarchitecture. Medial to the lateral ventricle is a piece of cortex that is folded onto itself in a peculiar shape. This structure is called the hippocampus, which, despite its bends, has only a single cell layer. (The term is from the Greek word for “seahorse.”) Connected to the hippocampus ventrally and laterally is another type of cortex that has only two cell layers. It is called the olfactory cortex because it is continuous with the olfactory bulb, which sits further anterior. The olfactory cortex is separated by a sulcus, called the rhinal fissure, from another more elaborate type of cortex that has many cell layers. This remaining cortex is called neocortex. Unlike the hippocampus and olfactory cortex, neocortex is found only in mammals. Thus, when we said previously that the cerebral cortex has expanded over the course of human evolution, we really meant that the neocortex has expanded. Similarly, when we said that the thalamus is the gateway to the cortex, we meant that it is the gateway to the neocortex. Most neuroscientists are such neocortical chauvinists (ourselves included) that the term cortex, if left unqualified, is usually intended to refer to the cerebral neocortex.


FIGURE 7.27 Three types of cortex in a mammal. In this section of a rat brain, the lateral ventricles lie between the neocortex and the hippocampus on each side. The ventricles are not obvious because they are very long and thin in this region. Below the telencephalon lies the brain stem. What region of brain stem is this, based on the appearance of the fluid-filled space at its core?

In Chapter 8, we will discuss the olfactory cortex in the context of the sense of smell. Further discussion of the hippocampus is reserved until later in this book, when we explore its role in the limbic system (Chapter 18) and in memory and learning (Chapters 24 and 25). The neocortex will figure prominently in our discussions of vision, audition, somatic sensation, and the control of voluntary movement in Part II, so let’s examine its structure in more detail.

Just as cytoarchitecture can be used to distinguish the cerebral cortex from the basal telencephalon, and the neocortex from the olfactory cortex, it can be used to divide the neocortex up into different zones. This is precisely what the famous German neuroanatomist Korbinian Brodmann did at the beginning of the twentieth century. He constructed a cytoarchitectural map of the neocortex (Figure 7.28). In this map, each area of cortex having a common cytoarchitecture is given a number. Thus, we have “area 17” at the tip of the occipital lobe, “area 4” just anterior to the central sulcus in the frontal lobe, and so on.


FIGURE 7.28 Brodmann’s cytoarchitectural map of the human cerebral cortex.

What Brodmann guessed, but could not show, was that cortical areas that look different perform different functions. We now have evidence that this is true. For instance, we can say that area 17 is visual cortex, because it receives signals from a nucleus of the thalamus that is connected to the retina at the back of the eye. Indeed, without area 17, a human is blind. Similarly, we can say that area 4 is motor cortex because neurons in this area project axons directly to the motor neurons of the ventral horn that command muscles to contract. Notice that the different functions of these two areas are specified by their different connections.

Neocortical Evolution and Structure-Function Relationships. A problem that has fascinated neuroscientists since the time of Brodmann is how the neocortex has changed over the course of mammalian evolution. The brain is a soft tissue, so there is not a fossil record of the cortex of our early mammalian ancestors. Nonetheless, considerable insight can be gained by comparing the cortex of different living species (see Figure 7.1). The surface area of the cortex varies tremendously among species; for example, a comparison of mouse, monkey, and human cortex reveals differences in size on the order of 1:100:1000. On the other hand, there is little difference in the thickness of the neocortex in different mammals, varying by no more than a factor of two. Thus, we can conclude that the amount of cortex has changed over the course of evolution, but not its basic structure.

The famous Spanish neuroanatomist Santiago Ramon y Cajal, introduced in Chapter 2, wrote in 1899 that “while there are very remarkable differences of organization of certain cortical areas, these points of difference do not go so far as to make impossible the reduction of the cortical structure to a general plan.” A challenge that has preoccupied many scientists since then has been to figure out exactly what this plan is. As we will discuss in later chapters, modern thinking is that the smallest functional unit of the neocortex is a cylinder of neurons 2 mm high—the distance from the white matter to the cortical surface—and 0.5 mm in diameter. This cylinder, usually described as a neocortical column, contains on the order of 10,000 neurons and 100 million synapses (approximately 10,000 synapses per neuron). We wish to understand the detailed wiring diagram of how these neurons connect with one another: the connectome of the neocortex. This is a tall order because synapses can be identified with confidence only using electron microscopy, which requires very thin (~50 nm) sections of tissue. To give an idea of the magnitude of the challenge, consider the project that South African Nobel laureate Sidney Brenner and his collaborators conducted in the Laboratory of Molecular Biology at the National Institute for Medical Research at Mill Hill, in North London, England. Brenner was convinced that understanding the neural basis of behavior required a circuit diagram, and to tackle this, he chose a simple organism, the 1 mm long flatworm, Caenorhabditis elegans (usually abbreviated C. elegans)—a far cry from the neocortex, granted, but possibly a tractable problem to solve because the worm has only 302 neurons and about 7000 synapses. Despite this relative simplicity, the “mind of the worm,” as they called their project, took over a dozen years to complete. Since the publication of this work in 1986, many of the obstacles to reconstructing a synaptic wiring diagram have begun to yield to advances in technology, including automated sectioning of brain tissue for electron microscopy and computer-aided reconstruction of volumes of tissue from very thin sections (Box 7.5). Although we are not there yet, such advances have spawned optimism that Cajal’s dream might soon be realized and not just for the cortex but for the entire brain.

My career path has been full of zigs and zags. When I was close to completing my Ph.D. in theoretical physics, my advisor sent me to Bell Laboratories in New Jersey for a summer job. As the famous research and development arm of the telecommunication company AT&T, Bell Labs had produced Nobel Prize–winning discoveries and seminal inventions like the transistor. During my summer there, I was supposed to theorize about superconductivity. Instead, I met Haim Sompolinsky, who had just arrived from Israel for a sabbatical year. Haim had previously developed mathematical models of interacting particles in a magnetic field and was now enthusiastically moving on to interacting neurons. I was hooked by this theory of neural networks, so I followed Haim to Jerusalem for post-doctoral training. We applied ideas from statistical physics to understand when artificial neural networks—that is, networks of computational units modeled loosely after neurons—learn not gradually but suddenly, as if with an “aha!” moment. When not engaged in lengthy mathematical calculations, I also learned to speak Hebrew and how to make hummus.

After two years in Jerusalem, I returned to Bell Labs. In the organizational chart, all company departments had a five-digit number. I belonged to Theoretical Physics, Department 11111. That meant we were the smartest of the smart, right? But Bell Labs was under pressure to be useful—to produce not Nobel Prizes but more revenue for AT&T—and some quipped, “The more 1’s in your department number, the more useless you are.”

Still, Bell Labs was like Disneyland for the mind, jam-packed with researchers working on a dizzying variety of interesting topics. Many left their office doors open, so you could pop in and ask questions any time. Experimental physicists in the Biological Computation Department were pioneering the use of functional MRI and advanced microscopy to observe neural activity. At the other end of the building were computer scientists working in the field of machine learning—a process by which a computer can “learn” from experience rather than being explicitly programmed.

Soon I was inventing algorithms that enabled artificial neural networks to learn, and I developed a mathematical theory of a hindbrain neural circuit called the oculomotor integrator. I continued this work after moving to the Massachusetts Institute of Technology as an assistant professor. In 2004, I was tenured and promoted to the rank of full professor. I should have been happy, but instead, I felt depressed. My theory of the oculomotor integrator was interesting and even plausible, judging from experimental tests by my collaborator David Tank at Princeton. But others were continuing to propose alternative theories, and the field showed no sign of converging on a consensus. My theory assumed the existence of recurrent connections between integrator neurons. Yet after a decade of study, I didn’t even know for sure whether integrator neurons were connected to each other at all!

When I complained to David, he suggested that I change my research focus. In the 1990s, we had both worked at Bell Labs with Winfried Denk, who had since moved to the Max Planck Institute of Biomedical Research in Heidelberg. There Winfried had built an ingenious automated device that could image the face of a block of brain tissue, and then shave off a thin slice to expose a new face. By repeatedly cutting deeper and deeper into the block, the device could acquire a three-dimensional (3D) image of brain tissue. Because Winfried’s device used an electron microscope, the image was sharp enough to reveal all synapses, as well as all neurons in the tissue. (Recall that Cajal could visualize only a small number of neurons with his light microscope and the Golgi stain, and could not see synapses at all.) In principle, from such an image it would be possible to reconstruct the “wiring diagram” of a piece of brain tissue by tracing the paths of neural branches, the “wires” of the brain, and locating the synapses.

The catch was the huge amount of image data that had to be analyzed. Winfried’s device had the potential to generate a petabyte of data from a cubic millimeter volume, the equivalent of a billion pictures in your digital photo album. Manual reconstruction of the wiring diagram would be prohibitively time-consuming. I decided to work on the problem of speeding up image analysis by computer automation. In 2006, my laboratory began collaborating with Winfried’s laboratory to apply the methods of machine learning to his images. This computational method significantly improved the speed and accuracy of 3D reconstruction of neurons. However, the method still made errors, so it could not completely replace human intelligence. In 2008, we started creating software that would enable humans to work with the machines to reconstruct neural circuits. This eventually turned into the “citizen science” project called EyeWire, which has registered over 150,000 players from 100 countries since its 2012 launch (http://blog.eyewire.org/about). “EyeWirers” analyze images by playing a game resembling a 3D coloring book. By coloring, they reconstruct the branches of neurons, which are like the “wires” of the brain (Figure A).


Figure A Seven neurons in a small volume of retina with their dendrites reconstructed from electron microscopic images. The neurites belonging to each neuron are colored differently. (Source: Courtesy of Dr. Sebastian Seung, Princeton University, and Kris Krug, Pop Tech.)

In 2014, Nature published the first EyeWire-assisted discovery: a new wiring diagram for a neural circuit in the retina. The discovery suggests a new solution to a problem that has eluded neuroscientists for 50 years: How does the retina detect moving visual stimuli? Researchers are conducting experiments to test our new theory, and only time will tell whether it’s correct. But it’s already clear that our computational technologies for reconstructing connectivity are accelerating progress towards understanding how neural circuits function. I'm now at the Princeton Neuroscience Institute, where I am continuing to work towards my dream of reconstructing a connectome, a wiring diagram of an entire brain.

Brodmann proposed that neocortex expanded by the insertion of new areas. Detailed comparisons of cortical structure and function in living species with diverse evolutionary histories suggest that the primordial neocortex of our common mammalian ancestor consisted mainly of three types of cortex. The first type consists of primary sensory areas, which are the first to receive signals from the ascending sensory pathways. For example, area 17 is designated as primary visual cortex, or V1, because it receives input from the eyes via a direct path: retina to thalamus to cortex. The second type of neocortex consists of secondary sensory areas, so designated because of their heavy interconnections with the primary sensory areas. The third type of cortex consists of motor areas, which are intimately involved with the control of voluntary movement. These cortical areas receive inputs from thalamic nuclei that relay information from the basal telencephalon and the cerebellum, and they send outputs to motor control neurons in the brain stem and spinal cord. For example, because cortical area 4 sends outputs directly to motor neurons in the ventral horn of the spinal cord, it is designated the primary motor cortex, or M1. It is believed that the common mammalian ancestor had on the order of about 20 different areas that could be assigned to these three categories.

Figure 7.29 shows views of the brain of a rat, a cat, and a human, with the primary sensory and motor areas identified. It is plain to see that when we speak of the expansion of the cortex in mammalian evolution, what has expanded is the region that lies in between these areas. Much of the “in-between” cortex reflects expansion of the number of secondary sensory areas devoted to the analysis of sensory information. For example, in primates that depend heavily on vision, such as humans, the number of secondary visual areas has been estimated to be between 20 and 40. However, even after we have assigned primary sensory, motor, and secondary sensory functions to large regions of cortex, a considerable amount of area remains in the human brain, particularly in the frontal and temporal lobes. These are the association areas of cortex. Association cortex is a more recent evolutionary development, a noteworthy characteristic of the primate brain. The emergence of the “mind”—our unique ability to interpret behavior (our own and that of others) in terms of unobservable mental states, such as desires, intentions, and beliefs—correlates best with the expansion of the frontal cortex. Indeed, as we will see in Chapter 18, lesions of the frontal cortex can profoundly alter an individual’s personality.


FIGURE 7.29 A lateral view of the cerebral cortex in three species. Notice the expansion of the human cortex that is neither strictly primary sensory nor strictly motor. Description

Although we have covered a lot of new ground in this chapter, we have only scratched the surface of neuroanatomy. Clearly, the brain deserves its status as the most complex piece of matter in the universe. What we have presented here is a shell, or scaffold, of the nervous system and some of its contents.

Understanding neuroanatomy is necessary for understanding how the brain works. This statement is just as true for an undergraduate first-time neuroscience student as it is for a neurologist or a neurosurgeon. In fact, neuroanatomy has taken on a new relevance with the advent of methods of imaging the living brain (Figure 7.30).


FIGURE 7.30 MRI scans of the authors. How many structures can you label?

An Illustrated Guide to Human Neuroanatomy appears as an appendix to this chapter. Use the guide as an atlas to locate various structures of interest. Labeling exercises are also provided to help you learn the names of the parts of the nervous system you will encounter in this book.

In Part II, Sensory and Motor Systems, the anatomy presented in this chapter and its appendix will come alive, as we explore how the brain goes about the tasks of smelling, seeing, hearing, sensing touch, and moving.

Gross Organization of the Mammalian Nervous System

1. Are the dorsal root ganglia in the central or peripheral nervous system?

2. Is the myelin sheath of optic nerve axons provided by Schwann cells or oligodendroglia? Why?

3. Imagine that you are a neurosurgeon, about to remove a tumor lodged deep inside the brain. The top of the skull has been removed. What now lies between you and the brain? Which layer(s) must be cut before you reach the CSF?

4. What is the fate of tissue derived from the embryonic neural tube? Neural crest?

5. Name the three main parts of the hindbrain. Which of these is also part of the brain stem?

6. Where is CSF produced? What path does it take before it is absorbed into the bloodstream? Name the parts of the CNS it will pass through in its voyage from brain to blood.

7. What are three features that characterize the structure of cerebral cortex?

Creslin E. 1974. Development of the nervous system: a logical approach to neuroanatomy. CIBA Clinical Symposium 26:1–32.

Johnson KA, Becker JA. The whole brain atlas. http://www.med.harvard.edu/AANLIB/home.html.

Krubitzer L. 1995. The organization of neocortex in mammals: are species really so different? Trends in Neurosciences 18:408–418.

Nauta W, Feirtag M. 1986. Fundamental Neuroanatomy. New York: W.H. Freeman.

Seung S. 2012. Connectome: How the Brain’s Wiring Makes Us Who We Are. Boston: Houghton Mifflin Harcourt.

Watson C. 1995. Basic Human Neuroanatomy: an Introductory Atlas, 5th ed. New York: Little, Brown & Co.

An Illustrated Guide to Human Neuroanatomy

(d) Major Sensory, Motor, and Association Areas of Cortex

Cross Section 1: Forebrain at Thalamus–Telencephalon Junction

Cross Section 3: Forebrain at Thalamus–Midbrain Junction

The Dorsal Surface of the Spinal Cord and Spinal Nerves

As we will see in the remainder of the book, a fruitful way to explore the nervous system is to divide it up into functional systems. Thus, the olfactory system consists of those parts of the brain that are devoted to the sense of smell, the visual system includes those parts that are devoted to vision, and so on. While this functional approach to investigating nervous system structure has many merits, it can make the “big picture”—how all these systems fit together inside the box we call the brain—difficult to see. The goal of this Illustrated Guide is to help you learn, in advance, about some of the anatomy that will be discussed in the subsequent chapters. Here, we concentrate on naming the structures and seeing how they are related physically; their functional significance is discussed in the remainder of the book.

The Guide is organized into six main parts. The first part covers the surface anatomy of the brain—the structures that can been seen by inspection of the whole brain, as well as those parts that are visible when the two cerebral hemispheres are separated by a cut in the midsagittal plane. Next, we explore the cross-sectional anatomy of the brain, using a series of slabs that contain structures of interest. The brief third and fourth parts cover the spinal cord and the autonomic nervous system. The fifth part of the Guide illustrates the cranial nerves and summarizes their diverse functions. The last part illustrates the blood supply of the brain.

The nervous system has an astonishing number of bits and pieces. In this Guide, we focus on those structures that will appear later in the book when we discuss the various functional systems. Nonetheless, even this abbreviated atlas of neuroanatomy yields a formidable list of new vocabulary. Therefore, to help you learn the terminology, an extensive self-quiz review is provided at the end, in the form of a workbook with labeling exercises.

Imagine that you hold in your hands a human brain that has been dissected from the skull. It is wet and spongy, and weighs about 1.4 kilograms (3 pounds). Looking down on the brain’s dorsal surface reveals the convoluted surface of the cerebrum. Flipping the brain over shows the complex ventral surface that normally rests on the floor of the skull. Holding the brain up and looking at its side—the lateral view—shows the “ram’s horn” shape of the cerebrum coming off the stalk of the brain stem. The brain stem is shown more clearly if we slice the brain right down the middle and view its medial surface. In the part of the guide that follows, we will name the important structures that are revealed by such an inspection of the brain. Notice the magnification of the drawings: 1× is life-size, 2× is twice life-size, 0.6× is 60% of life-size, and so on.


(a) Gross Features. This is a life-size drawing of the brain. Gross inspection reveals the three major parts: the large cerebrum, the brain stem that forms its stalk, and the rippled cerebellum. The diminutive olfactory bulb of the cerebrum can also be seen in this lateral view.


(b) Selected Gyri, Sulci, and Fissures. The cerebrum is noteworthy for its convoluted surface. The bumps are called gyri, and the grooves are called sulci or, if they are especially deep, fissures. The precise pattern of gyri and sulci can vary considerably from individual to individual, but many features are common to all human brains. Some of the important landmarks are labeled here. Notice that the postcentral gyrus lies immediately posterior to the central sulcus, and that the precentral gyrus lies immediately anterior to it. The neurons of the postcentral gyrus are involved in somatic sensation (touch; Chapter 12), and those of the precentral gyrus control voluntary movement (Chapter 14). Neurons in the superior temporal gyrus are involved in audition (hearing; Chapter 11).


(c) Cerebral Lobes and the Insula. By convention, the cerebrum is subdivided into lobes named after the bones of the skull that lie over them. The central sulcus divides the frontal lobe from the parietal lobe. The temporal lobe lies immediately ventral to the deep lateral (Sylvian) fissure. The occipital lobe lies at the very back of the cerebrum, bordering both parietal and temporal lobes. A buried piece of the cerebral cortex, called the insula (Latin for “island”), is revealed if the margins of the lateral fissure are gently pulled apart (inset). The insula borders and separates the temporal and frontal lobes.


(d) Major Sensory, Motor, and Association Areas of Cortex. The cerebral cortex is organized like a patchwork quilt. The various areas, first identified by Brodmann, differ from one another in terms of microscopic structure and function. Notice that the visual areas (Chapter 10) are found in the occipital lobe, the somatic sensory areas (Chapter 12) are in the parietal lobe, and the auditory areas (Chapter 11) are in the temporal lobe. On the inferior surface of the parietal lobe (the operculum) and buried in the insula is the gustatory cortex, devoted to the sense of taste (Chapter 8).



In addition to the analysis of sensory information, the cerebral cortex plays an important role in the control of voluntary, willful movement. The major motor control areas lie in the frontal lobe, anterior to the central sulcus (Chapter 14). In the human brain, large expanses of cortex cannot be simply assigned to sensory or motor functions. These constitute the association areas of cortex. Some of the more important areas are the prefrontal cortex (Chapters 21 and 24), the posterior parietal cortex (Chapters 12, 21, and 24), and the inferotemporal cortex (Chapters 24 and 25).

(a) Brain Stem Structures. Splitting the brain down the middle exposes the medial surface of the cerebrum, shown in this life-size illustration. This view also shows the midsagittal, cut surface of the brain stem, consisting of the diencephalon (thalamus and hypothalamus), the midbrain (tectum and tegmentum), the pons, and the medulla. (It should be noted that some anatomists define the brain stem as consisting only of the midbrain, pons, and medulla.) Description


(b) Forebrain Structures. Shown here are the important forebrain structures that can be observed by viewing the medial surface of the brain. Notice the cut surface of the corpus callosum, a huge bundle of axons that connects the two sides of the cerebrum. The unique contributions of the two cerebral hemispheres to human brain function can be studied in patients in which the callosum has been sectioned (Chapter 20). The fornix (Latin for “arch) is another prominent fiber bundle that connects the hippocampus on each side with the hypothalamus. Some of the axons in the fornix regulate memory storage (Chapter 24).

In the lower illustration, the brain has been tilted slightly to show the positions of the amygdala and hippocampus. These are “phantom views” of these structures since they cannot be observed directly from the surface. Both lie deep to the overlying cortex. We will see them again in cross section later in the Guide. The amygdala (from the Latin word for “almond”) is an important structure for regulating emotional states (Chapter 18), and the hippocampus is important for memory (Chapters 24 and 25). Description


(c) Ventricles. The lateral walls of the unpaired parts of the ventricular system—the third ventricle, the cerebral aqueduct, the fourth ventricle, and the spinal canal—can be observed in the medial view of the brain. These are handy landmarks because the thalamus and hypothalamus lie next to the third ventricle; the midbrain lies next to the aqueduct; the pons, cerebellum, and medulla lie next to the fourth ventricle; and the spinal cord forms the walls of the spinal canal.


The lateral ventricles are paired structures that sprout like antlers from the third ventricle. A phantom view of the right lateral ventricle, which lies underneath the overlying cortex, is shown in the lower illustration. The two cerebral hemispheres surround the two lateral ventricles. Notice how a cross section of the brain at the thalamus–midbrain junction will intersect the “horns” of the lateral ventricle of each hemisphere twice.

The underside of the brain has a lot of distinct anatomical features. Notice the nerves emerging from the brain stem; these are the cranial nerves, which are illustrated in more detail later in the Guide. Also notice the X-shaped optic chiasm, just anterior to the hypothalamus. The chiasm is the place where many axons from the eyes decussate (cross) from one side to another. The bundles of axons anterior to the chiasm, which emerge from the backs of the eyes, are the optic nerves. The bundles lying posterior to the chiasm, which disappear into the thalamus, are called the optic tracts (Chapter 10). The paired mammillary bodies (Latin for “nipple”) are a prominent feature of the ventral surface of the brain. These nuclei of the hypothalamus are part of the circuitry that stores memory (Chapter 24) and are a major target of the axons of the fornix (seen in the medial view). Notice also the olfactory bulbs (Chapter 8) and the midbrain, pons, and medulla.


(a) Cerebrum. The dorsal view of the brain is dominated by the large cerebrum. Notice the paired cerebral hemispheres. These are connected by the axons of the corpus callosum (Chapter 20), which can be seen if the hemispheres are retracted slightly. The medial view of the brain, illustrated previously, showed the callosum in cross section.


(b) Cerebrum Removed. The cerebellum dominates the dorsal view of the brain if the cerebrum is removed and the brain is tilted slightly forward. The cerebellum is an important motor control structure (Chapter 14), and is divided into two hemispheres and a midline region called the vermis (Latin for “worm”).


(c) Cerebrum and Cerebellum Removed. The top surface of the brain stem is exposed when both the cerebrum and the cerebellum are removed. The major divisions of the brain stem are labeled on the left side, and some specific structures are labeled on the right side. The pineal body, lying atop the thalamus, secretes melatonin and is involved in the regulation of sleep and sexual behavior (Chapters 17 and 19). The superior colliculus receives direct input from the eyes (Chapter 10) and is involved in the control of eye movements (Chapter 14), while the inferior colliculus is an important component of the auditory system (Chapter 11). (Colliculus is Latin for “mound.”) The cerebellar peduncles are the large bundles of axons that connect the cerebellum and the brain stem (Chapter 14).


Understanding the brain requires that we peer inside it, and this is accomplished by making cross sections. Cross sections can be made physically with a knife or, in the case of noninvasive imaging of the living brain, digitally with a magnetic resonance imaging or a computed tomography scan. For learning the internal organization of the brain, the best approach is to make cross sections that are perpendicular to the axis defined by the embryonic neural tube, called the neuraxis. The neuraxis bends as the human fetus grows, particularly at the junction of the midbrain and thalamus. Consequently, the best plane of section depends on exactly where we are along the neuraxis.

In this part of the Guide, we take a look at drawings of a series of cross-sectional slabs of the brain, showing the internal structure of the forebrain (cross sections 1–3), the midbrain (cross sections 4 and 5), the pons and cerebellum (cross section 6), and the medulla (cross sections 7–9). The drawings are schematic, meaning that structures within the slab are sometimes projected onto the slab’s visible surface.


Cross Section 1: Forebrain at Thalamus–Telencephalon Junction

(a) Gross Features. The telencephalon surrounds the lateral ventricles, and the thalamus surrounds the third ventricle. Notice that in this section, the lateral ventricles can be seen sprouting from the slit-like third ventricle. The hypothalamus, forming the floor of the third ventricle, is a vital control center for many basic bodily functions (Chapters 15–17). Notice that the insula (Chapter 8) lies at the base of the lateral (Sylvian) fissure, here separating the frontal lobe from the temporal lobe. The heterogeneous region lying deep within the telencephalon, medial to the insula and lateral to the thalamus, is called the basal forebrain.


(b) Selected Cell and Fiber Groups. Here, we take a more detailed look at the structures of the forebrain. Notice that the internal capsule is the large collection of axons connecting the cortical white matter with the brain stem, and that the corpus callosum is the enormous sling of axons connecting the cerebral cortex of the two hemispheres. The fornix, shown earlier in the medial view of the brain, is shown here in cross section where it loops around the stalk of the lateral ventricle. The neurons of the closely associated septal area (from saeptum, Latin for “partition”) contribute axons to the fornix and are involved in memory storage (Chapter 24). Three important collections of neurons in the basal telencephalon are also shown: the caudate nucleus, the putamen, and the globus pallidus. Collectively, these structures are called the basal ganglia and are an important part of the brain systems that control movement (Chapter 14).


(a) Gross Features. As we move slightly caudal in the neuraxis, we see the heart-shaped thalamus (Greek for “inner chamber”) surrounding the small third ventricle at the brain’s core. Just ventral to the thalamus lies the hypothalamus. The telencephalon is organized much like what we saw in cross section 1. Because we are slightly posterior, the lateral fissure here separates the parietal lobe from the temporal lobe.


(b) Selected Cell and Fiber Groups. Many important cell and fiber groups appear at this level of the neuraxis. One new structure apparent in the telencephalon is the amygdala, involved in the regulation of emotion (Chapter 18) and memory (Chapter 24). We can also see that the thalamus is divided into separate nuclei, of which two, the ventral posterior nucleus and the ventral lateral nucleus, are labeled. The thalamus provides much of the input to the cerebral cortex, with different thalamic nuclei projecting axons to different areas of cortex. The ventral posterior nucleus is a part of the somatic sensory system (Chapter 12) and projects to the cortex of the postcentral gyrus. The ventral lateral nucleus and closely related ventral anterior nucleus (not shown) are parts of the motor system (Chapter 14) and project to the motor cortex of the precentral gyrus. Visible below the thalamus are the subthalamus and the mammillary bodies of the hypothalamus. The subthalamus is a part of the motor system (Chapter 14), while the mammillary bodies receive information from the fornix and contribute to the regulation of memory (Chapter 24). Because this section also encroaches on the midbrain, a little bit of the substantia nigra (“black substance”) can be seen near the base of the brain stem. The substantia nigra is also a part of the motor system (Chapter 14). Parkinson’s disease results from the degeneration of this structure. Description


Cross Section 3: Forebrain at Thalamus–Midbrain Junction

(a) Gross Features. The neuraxis bends sharply at the junction of the thalamus and the midbrain. This cross section is taken at a level where the teardrop-shaped third ventricle communicates with the cerebral aqueduct. Notice that the brain surrounding the third ventricle is thalamus, and the brain around the cerebral aqueduct is midbrain. The lateral ventricles of each hemisphere appear twice in this section. You can see why by reviewing the phantom view of the ventricle, shown earlier.


(b) Selected Cell and Fiber Groups. Notice that this section contains three more important nuclei of the thalamus: the pulvinar nucleus and the medial and lateral geniculate nuclei. The pulvinar nucleus is connected to much of the association cortex and plays a role in guiding attention (Chapter 21). The lateral geniculate nucleus relays information to the visual cortex (Chapter 10), and the medial geniculate nucleus relays information to the auditory cortex (Chapter 11). Also notice the location of the hippocampus, a relatively simple form of cerebral cortex bordering the lateral ventricle of the temporal lobe. The hippocampus (Greek for “sea horse”) plays an important role in learning and memory (Chapters 24 and 25). Description


We are now at the midbrain, a part of the brain stem. Notice that the plane of section has been angled relative to the forebrain sections, so that it remains perpendicular to the neuraxis. The core of the midbrain is the small cerebral aqueduct. Here, the roof of the midbrain, also called the tectum (Latin for “roof”), consists of the paired superior colliculi. As discussed earlier, the superior colliculus is a part of the visual system (Chapter 10) and the substantia nigra is a part of the motor system (Chapter 14). The red nucleus is also a motor control structure (Chapter 14), while the periaqueductal gray is important in the control of the somatic pain sensations (Chapter 12). Description


The caudal midbrain appears very similar to the rostral midbrain. However, at this level, the roof is formed by the inferior colliculi (part of the auditory system; Chapter 11) instead of the superior colliculi. Review the dorsal view of the brain stem to see how the superior and inferior colliculi are situated relative to each other. Description


This section shows the pons and cerebellum, parts of the rostral hindbrain that border the fourth ventricle. As discussed earlier, the cerebellum is important in the control of movement. Much of the input to the cerebellar cortex derives from the pontine nuclei, while the output of the cerebellum is from neurons of the deep cerebellar nuclei (Chapter 14). The reticular formation (reticulum is Latin for “net”) runs from the midbrain to the medulla at its core, just under the cerebral aqueduct and fourth ventricle. One function of the reticular formation is to regulate sleep and wakefulness (Chapter 19). In addition, a function of the pontine reticular formation is to control body posture (Chapter 14). Description


As we move further caudally along the neuraxis, the brain surrounding the fourth ventricle becomes the medulla. The medulla is a complex region of the brain. Here, we focus only on those structures whose functions are discussed later in the book. At the very floor of the medulla lie the medullary pyramids, huge bundles of axons descending from the forebrain toward the spinal cord. The pyramids contain the corticospinal tracts, which are involved in the control of voluntary movement (Chapter 14). Several nuclei that are important for hearing are also found in the rostral medulla: the dorsal and ventral cochlear nuclei, and the superior olive (Chapter 11). Also shown are the inferior olive, important for motor control (Chapter 14), and the raphe nucleus, important for the modulation of pain, mood, and wakefulness (Chapters 12, 19, and 22). Description


The mid-medulla contains some of the same structures labeled in cross section 7. Notice, in addition, the medial lemniscus (Latin for “ribbon”). The medial lemniscus contains axons bringing information about somatic sensation to the thalamus (Chapter 12). The gustatory nucleus, a part of the larger solitary nucleus, serves the sense of taste (Chapter 8). The vestibular nuclei serve the sense of balance (Chapter 11).


As the medulla disappears, so does the fourth ventricle, now replaced by the beginning of the spinal canal. Notice the dorsal column nuclei, which receive somatic sensory information from the spinal cord (Chapter 12). Axons arising from the neurons in each dorsal column nucleus cross to the other side of the brain (decussate) and ascend to the thalamus via the medial lemniscus. Description


The Dorsal Surface of the Spinal Cord and Spinal Nerves

The spinal cord is situated within the vertebral column. The spinal nerves, a part of the somatic peripheral nervous system (PNS), communicate with the cord via notches between the vertebrae. The vertebrae are described based on where they are found. In the neck, they are called cervical vertebrae and are numbered from 1 to 7. The vertebrae attached to ribs are called thoracic vertebrae and are numbered from 1 to 12. The five vertebrae of the lower back are called lumbar, and those within the pelvic area are called sacral.

Notice how the spinal nerves and the associated segments of the spinal cord adopt the names of the vertebrae (see how eight cervical nerves are associated with seven cervical vertebrae). Also notice that the spinal cord in the adult human ends at about the level of the third lumbar vertebra. This disparity arises because the spinal cord does not grow after birth, whereas the spinal column does. The bundles of spinal nerves streaming down within the lumbar and sacral vertebral column are called the cauda equina (Latin for “horse’s tail”).


This view shows how the spinal nerves attach to the spinal cord and how the spinal meninges are organized. As the nerve passes into the vertebral notch, it splits into two roots. The dorsal root carries sensory axons whose cell bodies lie in the dorsal root ganglia. The ventral root carries motor axons arising from the gray matter of the ventral spinal cord. The butterfly-shaped core of the spinal cord is gray matter, consisting of neuronal cell bodies. The gray matter is divided into the dorsal, lateral, and ventral horns. Notice how the organization of gray and white matter in the spinal cord differs from that of the forebrain. In the forebrain, the gray matter surrounds the white matter; in the spinal cord, it is the other way around. The thick shell of white matter, containing the long axons that run up and down the cord, is divided into three columns: the dorsal columns, the lateral columns, and the ventral columns. Description


Illustrated in this view are some of the important tracts of axons running up and down the spinal cord. On the left side, the major ascending sensory pathways are indicated. Notice that the entire dorsal column consists of sensory axons ascending to the brain. This pathway is important for the conscious appreciation of touch. The spinothalamic tract carries information about painful stimuli and temperature. The somatic sensory system is discussed in Chapter 12. On the right side are some of the descending tracts important for the control of movement (Chapter 14). The names of the tracts accurately describe their origins and terminations (e.g., the vestibulospinal tract originates in the vestibular nuclei of the medulla and terminates in the spinal cord). Notice that the descending tracts contribute to two pathways: the lateral and ventromedial pathways. The lateral pathway carries the commands for voluntary movements, especially of the extremities. The ventromedial pathway participates mainly in the maintenance of posture and certain reflex movements. Description


In addition to the somatic PNS, which is devoted largely to the voluntary control of movement and conscious skin sensations, there is visceral PNS, devoted to the regulation of the internal organs, glands, and vasculature. Because this regulation occurs automatically and is not under direct conscious control, this system is called the autonomic nervous system, or ANS. The two most important divisions of the ANS are called the sympathetic and parasympathetic divisions.

The illustration shows the cavity of the body as it appears when it has been sectioned sagittally at the level of the eye. Notice the vertebral column, which is encased in a thick wall of connective tissue. The spinal nerves can be seen emerging from the column. Notice that the sympathetic division of the ANS consists of a chain of ganglia that runs along the side of the vertebral column. These ganglia communicate with the spinal nerves, with one another, and with a large number of internal organs. The parasympathetic division of the ANS is organized quite differently. Much of the parasympathetic innervation of the viscera arises from the vagus nerve, one of the cranial nerves emerging from the medulla. The other major source of parasympathetic fibers is the sacral spinal nerves. (The functional organization of the ANS is discussed in Chapter 15.)



Twelve pairs of cranial nerves emerge from the base of the brain. The first two “nerves” are actually parts of the CNS, serving olfaction and vision. The rest are like the spinal nerves, in the sense that they contain axons of the PNS. However, as the illustration shows, a single nerve often has fibers performing many different functions. Knowledge of the nerves and their diverse functions is a valuable aid in the diagnosis of a number of neurological disorders. It is important to recognize that the cranial nerves have associated cranial nerve nuclei in the midbrain, pons, and medulla. Examples are the cochlear and vestibular nuclei, which receive information from cranial nerve VIII. Most of the cranial nerve nuclei were not illustrated or labeled in the brain stem cross sections, however, because their functions are not discussed explicitly in this book. Description


Sensation of taste in anterior two-thirds of the tongue

Sensation of taste in posterior one-third of the tongue

Parasympathetic control of the heart, lungs, and abdominal organs

Two pairs of arteries supply blood to the brain: the vertebral arteries and the internal carotid arteries. The vertebral arteries converge near the base of the pons to form the unpaired basilar artery. At the level of the midbrain, the basilar artery splits into the right and left superior cerebellar arteries and the posterior cerebral arteries. Notice that the posterior cerebral arteries send branches, called posterior communicating arteries, that connect them to the internal carotids. The internal carotids branch to form the middle cerebral arteries and the anterior cerebral arteries. The anterior cerebral arteries of each side are connected by the anterior communicating artery. Thus, there is a ring of connected arteries at the brain’s base, formed by the posterior cerebral and communicating arteries, the internal carotids, and the anterior cerebral and communicating arteries. This ring is called the circle of Willis. Description


Notice that most of the lateral surface of the cerebrum is supplied by the middle cerebral artery. This artery also feeds the deep structures of the basal forebrain. Description


Most of the medial wall of the cerebral hemisphere is supplied by the anterior cerebral artery. The posterior cerebral artery feeds the medial wall of the occipital lobe and the inferior part of the temporal lobe. Description


This review workbook is designed to help you learn the neuroanatomy that has been presented. Here, we have reproduced the images from the Guide; however, instead of labels, numbered leader lines (arranged in a clockwise fashion) point to the structures of interest. Test your knowledge by filling in the appropriate names in the spaces provided. To review what you have learned, quiz yourself by putting your hand over the names. Experience has shown that this technique greatly facilitates the learning and retention of anatomical terms. Mastery of the vocabulary of neuroanatomy will serve you well as you learn about the functional organization of the brain in the remainder of the book.




(d) Major Sensory, Motor, and Association Areas of Cortex












Additional figures