The Structure of the Nervous System

INTRODUCTION GROSSORGANIZATION OF THE MAMMALIAN NERVOUSSYSTEM ANATOMICALREFERENCES THE CENTRALNERVOUS SYSTEM The Cerebrum The Cerebellum Ihe BroinStem The SpinolCord THE PERIPHERALNERVOUS SYSTEM Ihe SomoticPNS Ihe ViscerolPNS Afferentand EfferentAxons THECRANIAL NERVES THEMENINGES THEVENTRICULARSYSTEM r Box 7.1 Of SpecialInterest: Water on the Brain IMAGINGTHE LIVINGBRAIN ComputedTomogrophy MagneticResononce lmaging r Box 7.2 Brain Food:Magnetic Resonance Imaging FunctionolBroin lmaging r Box 73 Brain Food:Functional Imaging of Brain Activity: PETand fMRI UNDERSTANDINGCNS STRUCTURETHROUGH DEVELOPMENT FORMATIONOF THE NEURALTUBE r Box 7.4 Of SpecialInterest: Nutrition and the Neural TLrbe THREEPRIMARY BMIN VESICLES DIFFERENTIATIONOFTHE FOREBRAIN Differentiotionof theTelencepholon ond Diencephalon ForebroinStructure-F unction Relotionships DIFFERENTIATIONOFTHE MIDBRAIN MidbroinStructure-Function Relotionshrps DIFFERENTIATIONOFTHE HINDBRAIN HindbroinStructure-Function Relotionshrps DIFFERENTIATIONOFTHE SPINAL CORD SpinolCord Structure-Function Relotionshps PUTTINGTHE PIECESTOGETHER SPECIALFEATURES OF THE HUMANCNS A GUIDE TO THE CEREBRALCORTEX TYPESOF CEREBRALCORTEX AREASOF NEOCORTEX Neocortico/Evolution ond Structure-FunctionRelotionshrps r Box 7.5 Pathof Discovery:Evolution of My Brain, by Leah A. Krubitzer CONCLUDING REMARKS APPENDIX:AN ILLUSTRATEDGUIDE TO HUMAN NEUROANATOMY r68 CHAPTER 7 . THESTRUCTUREOFTHENERVOUSSYSTEM

V INTRODUCTION In previous chapters,we saw how individual neurons function and communicate. Now we are ready to assemblethem into a nervous systemthat sees,hears, feels, moves, remembers,and dreams.Just as an understanding of neuronal structureis necessaryfor understandingneuronal function, we must understandnervous system structure in order to understandbrain 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 appearscomplicated because it is distorted as a result of the selectivegrowth of some parts within the confinesof the skull. But once the basicmammalian plan is understood,these specializa- tions of the human brain becometransparent. We begin by introducing the genbral organization of the mammalian brain and the terms used to describeit. Then we take a look at how the three-dimensionalstructure of the brain arisesduring embryologicaland fetal development.Following the courseof developmentmakes it easierto understandhow the parts of the adult brain fit together.Finally, we explore the cerebralneocortex, a structure that is unique to mammals and pro- portionately the largest in humans. An Illustrated Guide to Human Neuroanatomyfollows the chapter as an appendix. The neuroanatomy presentedin this chapter providesthe canvason which we will paint the sensoryand motor systemsin Chapters8-14. Becauseyou will encounter a lot of new terms, self-quizzeswithin the chapter provide an opportunity for review.

V GROSSORGANIZATION OF THE MAMMALIAN NERVOUSSYSTEM The nervous systemof all mammalshas two divisions:the central nervous system(CNS) and the peripheralnervous system(PNS). In this section,we identify some of the important componentsof the CNS and the pNS. We also discussthe membranesthat surround the brain and the fluid-filled ventricleswithin the brain. We then explore some new methods of examining the structure of the living brain. But first, we need to review some anatomical terminology.

Anatomical References Getting to know your way around the brain is like getting to know your way around a city. To describeyour location in the city, you would use points of referencesuch as north, south, east,and west, up and down. The same is true for the brain, except that the terms-calle d anatomicalreferences-are different. Considerthe nervous systemof a rat (Figure 7.2a).We begin with the rat, becauseit is a simplified version that has all the general featuresof mammalian nervous system organization.In the head lies the brain, and the spinal cord runs down inside the backbonetoward the tail. The direction, or anatomicalreference, 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 dorsal (from the Latin for "back"), and the direction pointing down is ventral (from the Latin for "belly"). Thus, the rat Y GROSSORGANIZATION OFTHE MAMMALIAN NERVOUS SYSTEM I69

rIm

.:! Rat

Rabbit {ffi Cat

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FIGURE7.I Mammalian brains. Despitedifferences rn complexity,the brarnsof all these specieshave many featuresin common.The brainshave been drawn to appearapproximately the same stze; their relativesizes are shown in the inseton the left, t70 CHAPTER 7 . THESTRUCTUREOFTHENERVOUSSYSTEM

Spinal coro Dorsal

Anterior Posterior or rostral or caudal

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(a) Ventral FIGURE7,2 Basic anatomical references in the neryous system oi a rat. (a) Sideview. spinal cord runs anterior to posterior.The top side of the spinal cord is the (b) Top view. dorsalside, and the bottom side is the ventral side. If we look down on the nervous system,we seethat 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 characteristicis known as bilateralsymmetry. with just a few exceptions,most structureswithin the nervous systemcome in pairs, one on the right side and the other on the left. The invisible line running down the middle of the nervous systemis called the midline, and this gives us another way to describeanatomical references.structures closerto the midline are medial; structuresfarther away from the midline are lateral. In other words, the nose is medial to the eyes,the eyesare medial to the ears,and so on. In addition, rwo structures that are on the sameside are said to be ipsilateral to each other; for example,the right ear is ipsilateralto the right eye. If the structuresare on oppositesides of the midline, they are said to be contralateral to each other; the right ear is contralateralto the left ear. To view the internal structureof the brain, it is usually necessaryto slice it up. In the languageof anatomists,a slice is called a section;to slice is /o section.Although one could imagine an infinite number of ways we might cut into the brain, the standardapproach is to make cuts parallel to one of the three anatomicalplanes of section.The plane of the section resulting from splitting the brain into equal right and left halvesis calledthe midsagittal plane (Figure 7.3a). sectionsparallel to the midsagittalplane are in the sagittal plane. The two other anatomicalplanes are perpendicularto the sagittalplane and to one another. The horizontal plane is parallel to the ground (Figure 73b]'. A single sectionin this plane could passthrough both the eyesand the ears.Thus, horizontal sectionssplit the brain into dorsal and ventral parts. The coronal plane is perpendicularto the ground and to the sagittal plane (Figure 7.3c). A single section in this plane could passthrough both eyesor both ears,but not through all four at the sametime. Thus, the coronal plane splitsthe brain into anterior and posteriorparts.

v SELF-QUtZ Take a few moments right now and be sure you understand the meaning of theseterms:

anterior ventral contralateral rostral midline midsagittalplane posterior medial sagittal plane caudal lateral horizontal plane FIGURE7.3 dorsal ipsilateral coronal plane Anatomical planes of section. V GROSSORGANIZATION OFTHE MAMMALIAN NERVOUS SYSTEM t7l

The Central Nervous System The central nervous system (CNS) consistsof the parts of the nervous systemthat are encasedin bone: the brain and the spinal cord. The brain lies entirely within the skull. A sideview of the rat brain revealsthree parts that are common to all mammals:the cerebrum,the cerebellum,and the brain stem (Figure7.4a).

The Cerebrum. The rostral-most and largestpart of the brain is the cerebrum. Figure 7.4b showsthe rat cerebrumas it appearswhen viewed from above. Notice that it is clearly split down the middle into two cerebral hemispheres, separatedby the deepsagittal fissure.In general, the right cerebralhemisphere receivessensations from, and controls movements of, the left side of the body. Similarly, the left cerebralhemisphere is concernedwith sensationsand movements on the right side of the body.

The Cerebellum. Lying behind the cerebrum is the cerebellum (the wogd is derived from the Latin for "little brain"). While the cerebellumis in fact dwarfed by the large cerebrum, it actually contains as many neurons as both cerebralhemispheres combined. The cerebellumis primarily a movement control center that has extensiveconnections with the cerebrum and the spinalcord. In contrastto the cerebralhemispheres, the left sideof the cerebellum is concernedwith movementsof the left side of the body, and the right sideof the cerebellumis concernedwith movementsof the right side.

The Brain Stem. The remaining part of the brain is the brain stem, best observedin a midsagittalview of the brain (Figure7.4c\. The brain stem forms the stalk from which the cerebralhemispheres 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 consideredthe most primitive part of the mammalian brain, it is also the most important to life. One can survive damageto the cerebrum and cerebellum,but damageto the brain stem usually meansrapid death.

The Spinal Cord. The spinal cord is encasedin the bony vertebralcolumn and is attachedto the brain stem. The spinal cord is the major conduit of

Side(lateral) Midsagittal view: view:

(a) (c)

Cerebellum

Top (dorsal) view:

(b) FIGURE7.4 The brain of a rat. (a) Side(lateral) view. (b) Top (dorsal)view. (c) Midsagittalview. S:', ffi ,72 CHAPTER 7 . THESTRUCTUREOFTHENERVOUSSYSTEM {,3 \{ is s,sisr Sid a:{3 i*{ !f* $r{'aari l'$ F:I .-*l -qs 6!3 qiI S,rl ST ri\il ffi

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$i&l ffi B{ Spinal F{i Ventral nerves roots FIGURE7.5 The spinalcord. The spinal cord runs inside the vertebral column. Axons enter anc ex;1 thespinal cord via the dorsal and ventral roots, respectively.These rootscome tosether to formthe spinal nerves that course through the body

information from the skin,joints, and musclesof the body to the brain, and vice versa.A transectionof the spinal cord results in anesthesia(lack of feeling)in the skin and paralysisof the musclesin parts of the body caudal to the cut. Paralysisin this casedoes not mean that the musclescannot function but that they cannot be controlled by the brain. The spinal cord communicateswith the body via the spinal nerves, which are part of the peripheralnervous system (discussedbelow). Spinal nervesexit the spinal cord through notchesbetween each vertebra of the vertebral column. Each spinal nerve attachesto the spinal cord by means of two branches,the dorsal root and the ventral root (Figure7.5). Recall from chapter I that FrangoisMagendie showed that the dorsal root contains axons bringing information into the spinal cord, such as those that signalthe accidentalentry of a thumbtack into your foot (seeFigure 3.1). charles Bell showed that the ventral root contains axons carrying information awayfrom the spinal cord-for example, to the musclei that jerk your foot away in responseto the pain of the thumbtack.

The Peripheral Nervous System All the parts of the nervous system other than the brain and spinal cord comprisethe peripheral nervous system (pNS). The pNS has two parts: the somaticPNS and the visceralPNS.

The somatic PNS. All the spinalnerves that innervatethe skin, the joints, and the musclesthat are under voluntary control are part of the somatic PNS. The somaticmotor axons, which command muscle contraction,derive from motor neurons in the ventral spinal cord. The cell bodiesof the motor neurons lie within the cNS, but their axons are mostly in the pNS. The somaticsensory axons, which innervate and collect information from the skin, muscles,and joints, enter the spinalcord via the dorsalroots. The cell bodiesof theseneurons lie outsidethe spinalcord in clusterscalled V GROSSORGANIZATION OFTHE MAMMALIAN NERVOUS SYSTEM I73 dorsal root ganglia. There is a dorsalroot ganglion for each spinal nerve (seeFigure 7.5).

The Visceral PNS. The visceral PNS, also called the involuntary, vegeta- tive, or autonomic nervous system (ANS), consistsof the neurons that innervate the internal organs,blood vessels,and glands.Visceral sensory axons bring information about visceralfunction to the CNS, such as the pressureand oxygen content of the blood in the arteries.Visceral motor fibers command the contraction and relaxation of musclesthat form the walls of the intestinesand the blood vessels(called smooth muscles),the rate of cardiacmuscle contraction, and the secretoryfunction of various glands.For example,the visceralPNS controls blood pressureby 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, rememberthat when one speaksof an emotional reactionthat is. "butterflies beyond voluntary control-like in the stomach" or blushing- it usually is mediatedby the visceralPNS (the ANS).

Afferent and Efferent Axons. Our discussionof the PNSis a good place to introduce two terms that are usedto describeaxons 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. Considerthe axons in the PNS relative to a point of referencein the CNS. The somatic or visceral sensory axons bringing information into the CNSare afferents.The axonsthat emerge/roz the CNS to innervate the musclesand glandsare efferents.

The Cranial Nerves In addition to the nervesthat arisefrom 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 associatedwith it (originallynumbered by Galen,about 1800years ago, from anterior to posterior).Some of the cranial nervesare part of the CNS,others are part of the somaticPNS, and still others are part of the visceral PNS.Many cranial nerves contain a complex mixture of axons that perform different functions.The cranial nervesand their various functions are summarizedin the chapterappendix.

The Meninges The CNS,that part of the nervous systemencased 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 Greekfor "covering."The three membranesare the dura mater, the arachnoidmembrane, and the pia mater (Figure 7.6). The outermost covering is the dura mater, from the Latin words meaning "hard mother," an accuratedescription of the dura'sleatherlike 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 appearanceand a consistency resemblinga spider web. While there normally is no spacebetween the dura and the arachnoid,if the blood vesselspassing through the dura are ruptured,blood can collecthere and form what is calleda subduralhematoma. The buildup of fluid in this subdural space can disrupt brain function by 174 CHAPTER 7 . THESTRUCTUREOFTHENERVOUSSYSTEM

Duramater

Subdural space

Arachnoid membrane Subarachnoid space

Plamater

Artery

Brain

(b)

FIGURE7.6 The meninges.(a)The skullhas been removedto showthe tough outer meninseal membrane,the dura mater:(Source: Gluhbegoric and Williams, 1980.) (b) lllustrateiin cross section,the three meningeallayers protecting the brain and spinalcord are the dura mater: the arachnoidmembrane, and the pia mater:

compressingparts of the cNS. The disorderis treated by drilling a hole in the skull and draining the blood. "gentle The pia mater, the mother," is a thin membrane that adheres Choroid Subarachnoid closelyto the surfaceof the brain. Along the pia run many blood vessels plexus space that ultimately dive into the substanceof the underlying brain. The pia is separatedfrom the arachnoidby a fluid-filled space.This subarachnoidspace 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.

The Ventricular System In chapter l, we noted rhat the brain is hollow. The fluid-filled cavernsand canalsinside the brain constitutethe ventricular system. The fluid that runs in this systemis cSF,the sameas the fluid in the subarachnoidspace. cSF is producedby a specialtissue, called the choroid plexus,in the venrri- clesof the cerebralhemispheres. cSF flows from the pairedventricles of the cerebrumto a seriesof connected,unpaired cavities at the core of the brain stem (Figure7.7). csF exits the ventricularsystem and entersthe subarachnoid spaceby way of small openings,or apertures,located near where the cerebellumattaches to the brain stem. Ventricles In the subarachnoidspace, cSF is in brain absorbedby the blood vesselsat specialstructures called arachnoid villi. If the normal flow of CSFis disrupted,brain damagecan result (Box 7.1). we will return to fill in some details about the ventricular systemin a FIGURE7.7 moment. As we will see,understanding the organizationof the ventricu- The ventricular system in a rat brain. Iar system holds the key to understandinghow the mammalian brain is CSFis produced in the ventriclesof the organized. pairedcerebral hemispheres and flows through a seriesof unpairedventricles at the core of the brain stem.CSF escapes into the lmaging the Living Brain subarachnoidspace via smallapertures near the baseofthe cerebellum.In the subarach- For centuries, anatomists have investigated the structure of the brain by noid space,CSF is absorbedinto the blood, removing it from the head, sectioning it in various planes, staining the Y GROSSORGANIZATION OFTHE MAMMALIAN NERVOUS SYSTEM t75

Water on the Brain

lf the flow of CSF from the choroid plexus through the ventricularsystem to the subarachnoidspace is impaired, the fluid will back up and causea swellingof the ventricles.This condition is calledhydrocepholus, meaning Tube insertedinto "water head." lateralventricle throughhole in Occasionally,babies are born with hydrocephalus.How- skull -+4 ever,because the skull is soft and not completelyformed, t the head will expand in responseto the increasedin- rJ, from damage.Often, this evt(ft.'n tracranialfluid, sparing the brain |\$l conditiongoes unnoticed until the sizeofthe headreaches enormousProPortions. In adults,hydrocephalus is a much more serioussitua- tion becausethe skull cannot expand,and intracranial pressureincreases as a result.The soft brain tissue is then compressed,impairing function and leadingto death "obstructive" if left untreated.Typically,this hydrocephalus Drainagetube, is also accompaniedby severeheadache, caused by the usuallyintroduced distentionof nerve endingsin the meninges.Treatment into peritonealcavity, consistsof insertinga tube into the swollenventricle and with extralength to allowfor growthof child drainingoff the excessfluid (FigureA).

FIGUREA

sections, and examining the stained sections. Much has been learned by this approach, but there are some limitations. Most obviously, the brain removed from the head is dead. This, to say the least,limits the usefulnessof this method for examining the brain, and for diagnosing neurological dis- orders, in living individuals. Neuroanatomy has been revolutionized by the introduction of exciting new methods that enable one to produce images of the living brain. Here we briefly introduce them.

Computed Tomography. Some types of electromagnetic radiation, like "radiopaque" X-rays,penetrate the body and are absorbedby various tissues. Thus, using X-ray-sensitivefilm, 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 computedtomography (CTl, 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 "cut.") tomographyis derived from the Greek for To accomplish this, an X-ray source is rotated around the head within the plane of the desired crosssection. On the other side of the head, in the trajectory of the X-ray beam, are sensitiveelectronic sensorsof X-irradiation. The information about relative "viewing" radiopacity obtained with different angles is fed to a computer

', i:i'r, ;r'1;.f '1:'';...:l 476 CHAPTER7 THESTRUCTURE OFTHE NERVOUS SYSTEM

that executesa mathematical algorithm on the data. The end result is a dig- ital reconstructionof the position and amount of radiopaquematerial within the plane of the slice.cr scansnoninvasively revealed, for the first time, the grossorganization of gray and white matter, and the position of the ventricles,in the living brain.

Magnetic Resonance Imaging. While still used widely, CT is gradually being replaced by a newer imaging method, called magneticresonance imaging (MRI),The advantagesof MRI are that it yields a much more detailed map of the brain than CT it doesnot require X-irradiation, and imagesof brain slicescan be made in any plane desired.MRI usesinformation about how hydrogen atoms in the brain respond to perturbations of a strong magneticfield (Box 7.21.Tl:e electromagneticsignals emitted by the atoms are detectedby an array of sensorsaround the head and fed to a powerful computerthat constructsa map of the brain. The information from an MRI scan can be used to build a strikingly detailed image of the whole brain.

Functional Brain Imaging. CT and MRI are extremely valuable for de- tecting structuralchanges in the living brain, such as brain swelling after a head injury and brain tumors. Nonetheless,much of what goeson in the brain-healthy or diseased-is chemical and electricalin nature, and not observableby simple inspectionof the brain's anatomy. Amazingly, however, even these secretsare beginning to yield to the newest imaging techniques. "functional The two imaging" techniques now in widespread use are positronemission tomography (PET) and functional magneticresonance imaging (fMRIl.While the technical detailsdiffer, both methods detecr changesin regionalblood flow and metabolismwithin the brain (Box 7.3). The basic principle is simple. Neurons that are active demand more glucoseand oxygen.The brain vasculatureresponds to neural activity by directingmore blood to the active regions.Thus, by detectingchanges in blood flow, pET and fMRI reveal the regions of brain that are most active under different circumstances. The advent of imaging techniques has offered neuroscientiststhe ex- traordinary opportunity of peering into the living, thinking brain. As you can imagine, however, even the most sophisticatedbrain imagesare use- lessunless you know what you are looking at. Next, let's take a closerlook at how the brain is organized.

v SELF-QU|Z Tlakea few moments right now and be sure you understandthe meaning of theseterms: centralnervous system (CNS) dorsalroot ganglia brain visceralPNS spinal cord autonomic nervous system (ANS) cerebrum afferent cerebral hemispheres efferent cerebellum cranialnerve brain stem meninges spinalnerve dura mater dorsal root arachnoidmembrane ventral root pia mater peripheralnervous system (PNS) cerebrospinalfluid (CSF) somatic PNS ventricular system i, GROSSORGANIZATION OFTHE MAMMALIAN NERVOUS SYSTEM 177

Magnetic ResonanceImaging

Magneticresononce imaging (MRl) is a general technique lf we usedthe proceduredescribed above, we would that can be used for determiningthe amount of certain simply get a measurementof the total amount of hy- atoms at different locationsin the body.lt has become an drogen in the head.However, it is possibleto measure important tool in neurosciencebecause it can be used hydrogenamounts at a fine spatialscale by taking ad- noninvasivelyto obtain a detailed picture of the nervous vantageof the fact that the frequency at which protons system,particularly the brain. emit energy is proportional to the sizeof the magnetic In the most commonform of MRl,the hydrogenatoms field. In the MRI machinesused in hospitals,the mag- are quantified-for instance,those located in water or fat netic fields vary from one side of the magnet to the in the brain.An important fact of physicsis that when a other.Thisgives a spatialcode to the radio wavesemit- hydrogenatom is put in a magneticfield, its nucleus(which ted by the protons: High-frequencysignals come from consistsof a singleproton) can exist in either of two hydrogenatoms near the strong side of the magnet,and states:a high-energystate or a low-energystate. Because low-frequencysignals come from the weak side of the hydrogenatoms are abundantin the brain,there are many magneE. protons in each state. The last step in the MRI processis to orient the gradi- The key to MRI is makingthe protons jump from one ent of the magnetat many differentangles relative to the state to the other. Energy is added to the protons by headand measurethe amount of hydrogen.lt takesabout passingan electromagneticwave (i.e., a radio signal) l5 minutes to make all the measurementsfor a typical through the headwhile it is positionedbetween the poles brain scan.A sophisticatedcomputer program is then of a large magnet.Whenthe radio signalis set at iust the used to make a single imagefrom the measurements, right frequency,the protons in the low-energy state will resultingin a picture of the distributionof hydrogenatoms absorb energyfrom the signaland hop to the high-energy in the head. state.The frequencyat which the protons absorb energy FigureA is an MRI imageof a lateral view of the brain is called the resonant frequency (hence the name mag- in a livinghuman. In FigureB, another MRI image,a slice netic resonance).When the radio signalis turned off, has been made in the brain.Notice how clearlyyou can some of the protons fall back down to the low-energy see the white and gray matter.This differentiationmakes state,thereby emittinga radio signalof their own at a par- it possibleto see the effectsof demyelinatingdiseases on ticular frequency.Thissignal can be picked up by a radio white matter in the brain. MRI imagesalso reveallesions receiver.Thestronger the signal,themore hydrogenatoms in the brain becausetumors and inflammationgenerally between the poles of the magnet. increasethe amount of extracellularwater.

Centralsulcus

FIGUREA FIGUREB t78 CHAPTER7 THESTRUCTURE OFTHE NERVOUS SYSTEM

Functional Imaging of Brain Activity: PET and fMRr

Until recently,"mindreading" has been beyond the reachof Compilingthese measurementsproduces an imageof the science.However, with the introduction of positronemission brain activity pattern.The researchermonitors brain activity tomogrophy(PEI) and funaionol mognetic resononceimaging while the subject performs a task, such as moving a finger "light (fMRl),it is now possibleto observe and measurechanges or readingaloud. Different tasks up" differentbrain in brainactivity associated with the planningand execution areas.In order to obtain a picture of the activity inducedby of specifictasks, a particular behavioralor thought task,a subtraction tech- PET imagingwas developedin the 1970sby two groups nique is used.Even in the absenceof any sensorystimula- of physicists,one at WashingtonUniversity led by M. M. tion, the PET imagewill contain a great deal of brain activ- Ter-Pogossianand M. E. Phelps,and a second at UCLA led ity.To create an imageof the brain activity resultingfrom a by Z.H. Cho.Thebasic procedure is very simple.Aradioac- specifictask, such as a person looking at a picture,this back- tive solution containingatoms that emit positrons (posi- ground activity is subtractedout (FigureB). tively chargedelectrons) is introducedinto the bloodstream. Although PET imaginghas proven to be a valuabletech- Positrons,emitted wherever the blood goes,interact with nique,it hassignificant limitations. Because the spatialreso- electronsto produce photons of electromagneticradiation. lution is only 5- l0 mm3,the imagesshow the activityof many The locationsof the positron-emittingatoms are found by thousandsof cells.Also, a singlePET brain scan may take detectorsthat pick up the photons. one to many minutesto obtain.This, along with concerns One powerful applicationof PET is the measurementof about radiationexposure, limits the number of obtainable metabolicactivity in the brain.In a techniquedeveloped by scansfrom one person in a reasonabletime period.Thus, LouisSokoloff and his colleaguesat the National Instituteof the work of S. Ogawa at Bell Labs,showing that MRI tech- Mental Health,a posirron-emittingisotope of fluorine or niquescould be used to measurelocal changesin blood oxygen is attachedto 2-deoxyglucose(2-DG).This radioac- oxygen levelsthat result from brain activity,was an impor- tive 2-DG is injectedinto the bloodstream,and it travelsto tant advance. the brain.Metabolically active neurons, which normallyuse The fMRl method takes advantageof the fact that oxy- glucose,also take up the 2-DG.The2-DG is phosphorylated hemoglobin(the oxygenatedform of hemoglobinin the by enzymesinside the neuron,and this modificationprevents blood) has a differentmagnetic resonance than deoxyhe- the 2-DG from leaving.Thus, the amount of radioactive moglobin(hemoglobin that has donatedits oxygen).More 2-DG accumulatedin a neuron,and the numberof positron active regionsof the brain receivemore blood, and this emissions,indicate the level of neuronal metabolic activity. blood donates more of its oxygen.Functional MRI detects In a typicalPET application, a person'shead is placedin the locationsof increasedneural activity by measuring an apparatussurrounded by detectors (FigureA). Using the ratio of oxyhemoglobinto deoxyhemoglobin.lt has computeralgorithms, the photons(resulting from positron emergedas the method of choicefor functionalbrain im- emissions)reaching each of the detectors are recorded. agingbecause the scanscan be maderapidly (50 msec),they With this information,levels of activity for populationsof havegood spatialresolution (3 mm3),and they are com- neuronsat varioussites in the brain can be calculated. pletelynoninvasive.

C UNDERSTANDINGCNS STRUCTURE THROUGH DEVELOPMENT

The entire cNS is derivedfrom the walls of a fluid-filledtube that is formed at an early stage in embryonic development. The tube itself becomes the adult ventricular system.Thus, by examining how this tube changesdur- ing the courseof fetal development,we can understandhow the brain is organized and how the different parts fit together. In this section,we focr,rs on developmentas a way 1o understandthe structuralrlrganization of the brain. In Chapter 23, we will revisit the topic of developmentto see how neurons are born, how they find their way to their final krcations in the UNDERSTANDINGCNS STRUCTURETHROUGH DEVELOPMENT 179

i,;4-t*asdffiP

FIGUREA ThePET procedure. (Source: Posner and Raichle, 1994, p. 6l.)

' ffi ffi

FIGUREB A PET mage.(Source: Posner and Rarche, 199a,p.65.)

CNS, and I'tow they lnake the appropriatesynaptic c()lltccti()ns with onc anolhcr. As yur-rwork yollr way through this section,and through the rest of the book, yor-rwill encollnter many different narnesused by anatr)nliststo relcr 1tt groups of related neurons and axons. Sonte cornmon l-]amcsfor describingcollections o[ neuronsand axonsare givenin Tables7.1 and7.2. Take a lew rnoments to familiarizeyourself with these new terms belore continuing. Anatorny by itself can be pre11ydry. It really comes alive only alter rlre functionsof differentslrllctures are understood.The remainderof tl"risbook I80 cHAprER 7 . THEsrRUcruREoFTHENERVoussysrEM

Table7. I Collections of Neurons

NAME DESCRIPTIONAND EXAMPLE

Gray matter A genericterm for a collectionof neuronalcell bodiesin the CNS.When a freshlydissected brain is cut oPen,neurons aPPear gray. Cortex Any collection of neuronsthat form a thin sheet,usually at the brain'ssurface. Cortex is Latin for ;'bark." Example:cerebral cortex, the sheet of neurons found just under the surfaceof the cerebrum. Nucleus A clearlydistinguishable mass of neurons,usually deep in the brain (not to be confusedwith the "nut." nucleusof a cell).Nucleus is from the Latin word for Example;loterol geniculote nucleus, a cell Subs'can'ca^group in the brain stem that relaysinformation from the eye to the cerebral cortex. :::i3?Til[:ffiffiffi:ti*#jffI',::il::l'l#:1"::iTffi"::*::i:^;L:l?:' volved in the control of voluntary movement. "blue Locus A small,well-defined group of cells.Example:locus coeruleus (Latin for spot"),a brain stem cell (plural:loci) group involvedin the control of wakefulnessand behavioralarousal. "knot." Ganglion A collection of neurons in the PNS.Gonglion is from the Greek for Example:the dorsolroot (plural:ganglia) gonglio,which containthe cellsbodies of sensoryaxons entering the spinalcord via the dorsalroots. Only one cell group in the CNS goesby this name:the bosolgonglio, which are structureslying deep within the cerebrumthat control movement.

is devotcd to explainingthe functional organizationol the nerv

Formation of the NeuralTube

The embryo begir-rsas a flat disk with three'clistinctlayers ol cells callecl endoderm,mesoden-n, and ectoderm.The endodermultimate ly givesrisc to the lining of n-ranyof the internal urgans (visccra).Fror.n the mesldertnarisc the bonesof the skeletonand the n-ruscles.The nervor.lssystem ancl thc skin derive entirelv from the ectoderm. Our focusis on changesin the part of the ectoderntthat givesrise til the nervous system:rhe neuralplate. At this early stage (abotrt l7 days front

Table7.2 Collections of Axons NAME DESCRIPTIONAND EXAMPLE

Nerve A bundleof axonsin the PNS.Only one collectionof CNS axonsis calleda nerve:the optic nerve. White matter A genericterm for a collectionof CNS axons.Whena freshlydissected brain is cut open,axons appearwhite. Tract A collectionof CNS axonshaving a common site of origin and a common destination.Example: corticospinoltroct, which originatesin the cerebral cortex and ends in the spinalcord. Bundle A collectionof axonsthat run toSetherbut do not necessarilyhave the sameorigin and destination. Example:mediol forebroin bundle, which connectscells scatteredwithin the cerebrum and brain stem. Capsule A collection of axons that connect the cerebrum with the brain stem. Example:internol copsule, which connectsthe brain stem with the cerebral cortex. Commissure Any collectionof axonsthat connectone sideof the brainwith the other side. Lemniscus A tract that meandersthrough the brain like a ribbon. Example:mediol lemniscus, which bringstouch informationfrom the spinalcord throughthe brain stem. v uNDERsrANDrNGcNssrRUcruRETHRoucHDEVELopMENT l8l

Rostral

Caudal Neural Neural Somites Neural Neural fold tube crest tube

Endoderm FIGURE7.8 Formationof the neuraltube and neuralcrest.These schematic illustrations follow theearly development of the nervous system in the embryo.The drawings above are dorsal viewsof theembryo; those below are cross sections. (a) The primitive embryonic CNS beginsas a thinsheet of ectoderm.(b)The first important step in the development of the nervoussystem is the formationof the neuralgroove. (c) Thewalls of the groove,called neuralfolds, come together and fuse, forming the neural tube. (d) Thebits of neuralecto- dermthat are pinched off when the tube rolls up is called the neural crest, from which the PNSwill develop.The somites are mesoderm that will sive rise to muchof theskeletal systemand the muscles.

conceptionin humans), the brain consistsonly of a flat sheetof cells (Fig- ure 7.8a). The next event of interest is the formation of a groove in the neural plate that runs rostral to caudal, called the neuralgroove (Figure 7.8b). The walls of the groove are called neuralfolds, which subsequently move together and fuse dorsally,forming the neural tube (Figure 7.8c). Theentire central nervous system develops from the walls of the neural tube.As the neural folds come together,some neural ectodermis pinched off and comes to lie just lateral to the neural tube. This tissueis called the neural crest (Figure 7.8d). All neuronswith cellbodies in theperipheral nervous system derive from the neural crest. The neural crest develops in close associationwith the underlying mesoderm.The mesodermat this stagein developmentforms prominent bulgeson either side of the neural tube calledsomites. From these somites, the 33 individual vertebraeof the spinal column and the related skeletal muscleswill develop.The nervesthat innervate these skeletalmuscles are therefore called somaticmotor nerves. The processby which the neural plate becomesthe neural tube is called neurulation. Neurulation occurs very early in embryonic development, abott 22 days after conceptionin humans. A common birth defect is the I82 CHAPTER7 THESTRUCTURE OFTHE NERVOUS SYSTEM

Nutrition and the Neural Ti.rbe

Neuraltube formationis a crucialevent in the development sultsin onencephaly,a condition characterized by degenera- of the nervous system.lt occurs early-only 3 weeks after tion of the forebrainand skull that is alwaysfatal. Failure conception-when the mother may be unawareshe is preg- of the posterior neuraltube to closeresults in a condition nant.Failure of the neuraltube to close correctly is a calledspino bifida. ln its most severeform, spinabifida is common birth defect,occurring in approximatelyI out of characterizedby the failureof the posterior spinalcord to every500 livebirths. A recentdiscovery of enormouspub- form from the neural plate (bifdo is from the Latin word "cleft lic healthimportance is that many neuraltube defectscan meaning in two parts").Less severe forms are char- be traced to a deficiencyof the vitamin folicocid (or Blote) acterizedby defectsin the meningesand vertebraeoverly- in the maternal diet during the weeks immediatelyafter ing the posterior spinalcord. Spina bifida, while usuallynot conception.lt has been estimatedthat dietary supplemen- fatal,does requireextensive and costlymedical care. tation of folic acidduring this period could reducethe inci- Folicacid plays an essentialrole in a numberof metabolic dence of neural tube defectsby 90%. pathways,including the biosynthesisof DNA, which natu- Formation of the neural tube is a complex process rally must occur during developmentas cellsdivide. Al- (FigureA). lt dependson a precisesequence of changesin thoughwe do not preciselyunderstand why folic acid defi- the three-dimensionalshape of individualcells, as well as on ciencyincreases the incidenceof neuraltube defects,one changesin the adhesionof each cell to its neighbors.The can easilyimagine how it could alter the complexchoreog- timingof neurulationalso must be coordinatedwith simul- raphy of neurulation.The name is derivedfrom the Latin "leaf," taneouschanges in non-neuralectoderm and the meso- word for reflectingthe fact that folic acid was first derm. At the molecularlevel, successful neurulation de- isolatedfrom spinachleaves. Besides green leafyvegetables, pends on specificsequences of gene expressionthat are good dietary sourcesof folic acid are liver,yeast, eggs, beans, controlled,in part,by the positionand localchemical envi- and oranges.Many breakfastcereals are now fortified with ronment of the cell.lt is not surprisingthat this processis folic acid.Nonetheless, the folic acid intakeof the average highlysensitive to chemicals,or chemicaldeficiencies, in the Americanis only half of what is recommendedto prevent maternalcirculation. birth defects (0.4 mg/day).The U.S.Centers for Disease The fusion of the neuralfolds to form the neuraltube Control and Preventionrecommends that women take mul- occurs first in the middle,then anteriorlyand posteriorly tivitaminscontaining 0.4 mg of folic acid before planning (FigureB). Failureof the anterior neuraltube to close re- PreSnancy.

FIGUREA > Scan^inge ectronmic'og.3p|5 of ^eu'-lator. (Sou'ce:Smith anc Schoe.rwoif,1997.;

failure of appropriateclosure of the neural tube. Fortunately,recent research suggeststhat most casesof neural tube defectscan be avoided by ensuring proper maternal nutrition during this period (Box 7.4).

Three Primary Brain Vesicles The processby which structures become more complex and functionally specializedduring development is called differentiation. The first step in the differentiation of the brain is the develoDment.ar rhe rostral end of the II UNDERSTANDINGCNS STRUCTURE THROUGH DEVELOPMENT r83

22 days 23 days Rostral I t ,,i, \t'0" ,\I

Caudal (a)

,) r I ): I itn rt ,S.r \ kS''i ht,'i 4Vu $v, -4) Anencephaly Spinabifida

FIGUREB 0.180mm (a) Neuraltube closure. (b) Neuraltube defects,

neural tube, of three swellingscalled the primary vesicles(Figure 7.91 . The entire brain derivesfrom the threeprimary vesiclesof the neural tube. The rostral-most vesicleis called the prosencephalon.Pro is Greek for "be- "brain." tore"; encephalonis derived from the Greek for Thus, the prosen- cephakrn 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 connectswith the caudal neural tube, which gives rise to the spinal cord. t84 CHAPTER7 THESTRUCTURE OFTHE NERVOUS SYSTEM

Rostral Difrerentiation of the Forebrain Prosencephalon or forebrain The next important developmentsoccur in the forebrain,where secondary vesiclessprout off on both sidesof the prosencephalon.The secondaryvesi- Mesencephalon cles are the opticvesicles and the telencephalicvesicles. The unpaired structure or midbrain that remains after the secondaryvesicles have sprouted off is called the diencephalon, or "between brain" (Figure 7.10). Thus, the forebrain at this stageconsists of the two optic vesicles,the two telencephalicvesicles, and the diencephalon. Rhombencephalon or hindbrain The optic vesiclesgrow and invaginate (fold in) to form the optic stalks and the optic cups, which will ultimately become the opticnerves and th.e two retinasin the adult (Figure7.1 I ). The important point is that the retina FIGURE7.9 at the back of the eye, and the optic nerve connectingthe eye to the dien- The three primary brain vesicles.The cephalon,are part of the brain, not the PNS. rostralend of the neuraltube differentiatesto Differentiation of the Telencephalon and Diencephalon. The telen- form the threevesicles that will giverise to "endbrain," the entirebrain.This view isfrom above,and cephalicvesicles together form the telencephalon, or consist- the vesicleshave been cut horizontallvso that ing of the two cerebralhemispheres. The telencephaloncontinues to de- we cansee the insideofthe neuraltube. velop in four ways: (l) The telencephalicvesicles grow posteriorly so that they lie over and lateral to the diencephalon(Figure 7.l2al. (2) Another pair of vesiclessprout off the ventral surfacesof the cerebralhemispheres, giving rise to the olfactory bulbs and related structuresthat participate . [t*.;il* in the senseof smell (Figure7.12b\. (3) The cellsof the walls of the te- lencephalondivide and differentiateinto various structures.(4) White ;"::;",". matter systemsdevelop, carrying axons to and from the neurons of the *El telencephalon. L_ory_":.1'':: Figure 7.I3 shows a coronal sectionthrough the primitive mammalian Midbrain forebrain, to illustrate how the different parts of the telencephalonand diencephalondifferentiate and fit together. Notice that the two cerebral hemisphereslie aboveand on either sideof the diencephalon,and that the ventral-medialsurfaces of the hemisphereshave fused with the lateral surfacesof the diencephalon(Figure 7.I3al. FIGURE7.IO The fluid-filled spaceswithin the cerebral hemispheresare called the The secondary brain vesiclesof the lateral ventricles, and the spaceat the center of the diencephalon is forebrain. The forebraindifferentiates into called the third ventricle (Figure 7.13b). The paired lateral ventricles the pairedtelencephalic and optic vesicles, and the diencephalon.Theoptic vesicles develop are a key landmark in the adult brain: Whenever you see paired fluid- into the eyes. filled ventricles in a brain section, you know that the tissue surrounding them is in the telencephalon.The elongated,slitlike appearanceof the third ventriclein crosssection is alsoa useful featurefor identifying the diencephalon. Cutedge of Notice in Figure 7.LJ that the walls of the telencephalicvesicles appear opticcup swollen due to the proliferation of neurons. Theseneurons form two different types of gray matter in the telencephalon:the cerebral cortex and the basal telencephalon. Likewise, the diencephalondifferentiates into two structures:the thalamus and the hypothalamus (Figure7.13c). The thalamus,nestled deep inside the forebrain, gets its name from the Greek word for "inner chamber." The neurons of the developingforebrain extend axons to communicate with other parts of the nervous system.These axons bundle together to form three major white matter systems:the corticalwhite matter, the cor- Cut edge of wall of diencephalon pus callosum,and the internal capsule(Figure 7.13d). The cortical white matter contains all the axons that run to and from the neurons in the FIGURE7.I I cerebralcortex. The corpus callosum is continuouswith the corticalwhite Early development of the eye. The optic matter and forms an axonal bridge that links cortical neurons of the two vesicledifferentiates into the ootic stalk and the optic cup.Theoptic stalkwill becomethe cerebralhemispheres. The corticalwhite matter is alsocontinuous with the optic nerve,and the optic cup will become internal capsule, which links the cortex with the brain stem, particularly the retrna. the thalamus. V UNDERSTANDINGCNS STRUCTURE THROUGH DEVELOPMENT r85

Telencephalon Dorsal Cerebral (2 cerebralhemispheres) hemispheres Rostral

Diencephalon

Midbrain

Hindbrain

Caudal Opticcups

(a) Differentiation (b) FIGURE7.I2 Difierentiationof the telencephalon.(a) As developmentproceeds, the cerebral hemispheresswell and grow posteriorly and laterally to envelopthe diencephalon. (b) Theolfactory bulbs sprout off the ventral surfaces of each telencephalic vesicle.

Forebrain Structure-Function Relationships. The forebrain is the seat of perceptions,conscious awareness, cognition, and voluntary action. All this dependson extensive interconnectionswith 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 expandedthe most over the courseof human evolution. Cortical neuronsreceive sensory information, form perceptionsof the outsideworld, and command voluntary movements. Neuronsin the olfactory bulbs receiveinformation from cellsthat sense chemicalsin the nose (odors)and relay this information caudallyto a part

Telencephalon Cerebralcortex Thalamus Hypothalamus Diencephalon Basaltelencephalon

Malndlvlslons (c) Graymatter structures ;.::"'ffi*ffllffi

(b) Ventrlcles (d) Whlte matterstructures FIGURE7.I3 Structural features of the forebrain. t86 CHAPTER 7 . THESTRUCTUREOFTHENERVOUSSYSTEM

Cerebral of the cerebralcortex for further analysis.Information from the eyes,ears, and skin is alsobrought to the cerebralcortex for analysis.However, each of the sensorypathways serving vision, audition (hearing), and somatic sensationrelays (i.e., synapsesupon neurons) in the thalamus en route to the cortex. Thus, the thalamus is often referred to as the gateway to the cerebralcortex (Figure7.I4). Thalamicneurons send axons to the cortex via the internal capsule.As a generalrule, the axons of each internal capsulecarry information to the cortex about the contralateralside 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 lelt foot is doing? One important way is by communication between the hemispheresvia the axons in the corpuscallosum. Cortical neurons also send axons through the internal capsule,back to the brain stem. Some cortical axons courseall the way to the spinal cord, forming the corticospinaltract. This is one important way cortex can Eye Ear Skin command voluntary movement. Another way is by communicatingwith FIGURE7.I4 neuronsin the basalganglia, a collectionof cellsin the basaltelencephalon. The thalamus: gateway to the cerebral The term basalis usedto describestructures deep in the brain, and the basal cortex. The sensorypathways from the eye, gangliaIie deepwithin the cerebrum.The functions of the basalganglia are ear:and skin all relayin the thalamusbefore poorly understood,but it is known that damageto thesestructures disrupts terminatingin the cerebralcortex.The arrows indicatethe directionof informationflow. 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 discussa structure called the amygdalathat is involved in fear and emotion. Although the hypothalamuslies just under the thalamus,functionally it is more closelyrelated to certain telencephalicstructures, like the amyg- dala. The hypothalamusperforms many primitive functions and therefore hasnot changedmuch over the courseof mammalianevolution. "Primitive" doesnot mean unimportant or uninteresting,however. The hypothalamus controls the visceral (autonomic) nervous system,which regulatesbodily functionsin responseto the needsof the organism.For example,when you are facedwith a threatening situation, the hypothalamusorchestrates the body's visceral fight-or-flight response.Hypothalamic commands to the ANS will lead to (among other things) an increasein the heart rate, in- creasedblood flow to the musclesfor escape,and even the standingof your hair on end. Conversely,when you're relaxing after Sunday brunch, the

v SELF-QUIZ Listedbelow are derivativesof the forebrain that we have discussed.Be sure vou know what each of these terms means. PRIMAtrVESICLE SECONDAWVESICLE SOME ADULT DERIVATIVES Forebrain Optic vesicle Retina (prosencephalon) Optic nerve Thalamus Dorsalthalamus (diencephalon) Hypothalamus Third ventricle Telencephalon Olfactorybulb Cerebralcortex Basaltelencephalon Corpuscallosum Cortical white matter Internalcapsule V UNDERSTANDING CNS STRUCTURE THROUGH DEVELOPMENT r87 hypothalamusensures that the brain is well-nourished via commandsto the ANS, which will increaseperistalsis (movement of material through the gastrointestinaltract) and redirect blood to your digestivesystem. The hypothalamus also plays a key role in motivating animals to find food, drink, and sex in responseto their needs.Aside from its connectionsto the ANS, the hypothalamusalso directsbodily responsesvia connectionswith the pituitary gland locatedbelow the diencephalon.This gland communicates to many parts of the body by releasinghormones into the bloodstream.

Difrerentiationof the Midbrain Unlike the forebrain, the midbrain differentiates relatively little during subsequentbrain development(Figure 7.I5.1.The dorsal surfaceof the mesencephalicvesicle becomes a structure called the tectum (Latin for "roof"). The floor of the midbrain becomesthe tegmentum. The CSF-filled spacein between constricts into a narrow channel called the cerebral aqueduct. The aqueductconnects rostrally with the third ventricle of the diencephalon.Because it is small and circular in crosssection, the cerebral aqueductis a good landmark for identifying the midbrain.

Midbrain Structure-Function Relationships. For such a seemingly simple structure,the functions of the midbrain are remarkablydiverse. Be- sidesserving as a conduit for information passingfrom the spinal cord to the forebrainand vice versa,the midbrain containsneurons that contribute to sensorysystems, the control of movement, and severalother functions. The midbrain containsaxons descendingfrom the cerebralcortex to the brain stem and the spinal cord. For example,the corticospinaltract courses through the midbrain en route to the spinal cord. Damageto this tract in the midbrain on one sideproduces a lossof voluntary control of movement on the oppositeside of the body. The tectum differentiatesinto two structures:the superiorcolliculus and the inferior colliculus.The superiorcolliculus receives direct input from the eye, so it is also calledthe optic tectum. One function of the optic tectum is to control eye movements,which it doesvia synapticconnections with the motor neurons that innervate the eve muscles.Some of the axons that

Ditferentiation

Cerebral aqueduct

Tegmentum FIGURE7.I5 Difrerentiation of the midbrain. The midbraindifferentiates into the tectumand the tegmentum.TheCSF-filled space at the coreof the midbrainis the cerebralaqueduct. (Drawingsare not to scale.) *1 st ffi r88 CHAPTER 7 . THESTRUCTUREOFTHENERVOUSSYSTEM Si \3 iifi .Y.'{ SrI supply the eye muscles originate in the midbrain, bundling together to $rr.f $:i form cranial nervesIII and IV (seethe chapter appendix). itsr The inferior colliculusalso receivessensory information, but from the ear r,{ instead of the eye. The inferior colliculus serves as an important relay TJ ${i station for auditory information en route to the thalamus. HS s4 The tegmentum is one of the most colorful regionsof the brain because iri it containsboth the substantianigra (the black substance)and the red "*i nucleus. These two cell groups are involved in the control of voluntary *r movement. Other cell groups scatteredin the midbrain have axons that U:i project widely throughout much of the CNS and function to regulatecon- $.1 sciousness,mood, pleasure,and pain. *;,t

wr.: ri g':'j Difrerentiationof the Hindbrain e-i The hindbrain differentiatesinto three important structures:the cerebellum, the pons, and the medulla oblongata-also called, simply, the H medulla. The cerebellum and pons develop from the rostral half of the BJ$$ hindbrain (calledthe metencephalon);the medulla developsfrom the caudal il;'l *':i half (calledthe myelencephalon).The CSF-filledtube becomesthe fourth iqt ventricle, which is continuouswith the cerebralaqueduct of the midbrain. K:l At the three-vesiclestage, the rostral hindbrain in crosssection is a {$i

simple tube. In subsequentweeks, the tissue along the dorsal-lateralwall tilH\! of the tube, calledthe rhombic lip, grows dorsallyand medially until it fuses with its twin on the other side.The resultingflap of brain tissuegrows into the cerebellum.The ventral wall of the tube differentiatesand swells to form the pons (Figure7.161. Lessdramatic changes occur during the differentiationof the caudalhalf of the hindbrain into the medulla. The ventral and lateral walls of this region swell, leavingthe roof coveredonly with a thin layer of non-neuronal ependymalcells (Figure7.I7). Along the ventral surfaceof each side of the medulla runs a major white matter system.Cut in crosssection, these

Forebrain

Midbrain

Hindbrain

Differentiation

Cerebellum

Fourth Rhombiclips ventricle

FIGURE7.I6 Difrerentiation of the rostral hindbrain. The rostral hindbrain diferentiates into the cerebellumand oons.Thecerebellum is formed by the growth and fusion of the rtrombiclips.The CSF-filled space at the core of the hindbrainis the fourth ventricle. (Drawingsare not to scale.) !r UNDERSTANDINGCNSSTRUCTURETHROUGHDEVELOPMENTI89

Forebrain

Midbrain

Hindbrain

Differentiation

Fourth ventricle

Medulla

Medullary pyramids

FIGURE7.I7 Difierentiation of the caudal hindbrain.The caudalhindbrain differentiates into the medulla.Themedullary pyramids are bundles of axonscoursing caudally toward the spinal cord.TheCSF-fllled space at the coreof the medullais the firurthventricle. (Drawings are not to scale,)

bundles of axons appear somewhat triangular in shape, explaining why they are called the medullary pyramids.

Hindbrain Structure-Function Relationships. Like the midbrain. rhe 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 ANS. "little The cerebellum, the brain," is an important movement control center. It receivesmassive 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 contrac- tions that are required to achieve the movement goals.Damage to the cerebellum results in uncoordinated and inaccurare movemenrs. Of the descendingaxons passingthrough the midbrain, more than 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 oppo- site site. Thus, the pons serves as a massive switchboard connecting the cerebral cortex to the cerebellum. (The word pons is from the Latin word "bridge.") for 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 cor- "pyramidal tex and are part of the corticospinal tract. Thus, tract" is often

ffi. 190 cHAPTER7 THESTRUCTURE OFTHE NERVOUS SYSTEM

used as a synonym for corticospinaltract. Near where the medulla joins with the spinal cord, eachpyramidal tract crossesfrom one sideof the midline to the other. A crossingof axons from one side to the other is known as a decussation,and this one is called the pyramidaldecussation The crossing of axons in the medulla explainswhy the cortex of one side of the brain controls movementson the oppositeside of the body (Figure 7.18). In addition to the white matter systemspassing through, the medulla contains neurons that perform many different sensory and motor functions. For example,the axons of the auditory nerves,bringing auditory Medulla information from the ears,synapse on cells in the cochlearnuclei of the medulla. The cochlearnuclei project axons to a number of different struc- Pyramidal decussation tures, including the tectum of the midbrain (inferior colliculus,discussed above).Damage to the cochlearnuclei leadsto deafness. Other sensoryfunctions of the medulla include touch and taste.The Soinalcord medulla containsneurons that relay somaticsensory information from the spinalcord to the thalamus.Destruction of the cellsleads 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 FIGURE7.I8 cellsthat control the tongue musclesvia cranial nerve XII. (So think of the The pyramidal decussation.The cortico- medulla the next time you stick out your tongue!) spinaltract crosses from one sideto the otherin the medulla. v SELF-QU|Z Listed below are derivatives of the midbrain and hindbrain that we have discussed.Be sure you know what each of these terms means. PRIMARYVESICLE SOMEADULT DERIVATIVES Midbrain(mesencephalon) Tectum Tegmentum Cerebralaqueduct Hindbrain(rhombencephalon) Cerebellum Pons Founhventricle Medulla

Difrerentiation of the Spinal Cord As shown in Figure 7.19, the transformationof the caudalneural tube into the spinal cord is straightforward compared to the differentiation of the brain. With the expansionof the tissuein the walls, the cavity of the tube constrictsto form the tiny CSF-filledspinal canal. Cut in crosssection, the graymatter of the spinalcord (wherethe neurons are) hasthe appearanceof a butterfly.The upper part of the butterfly'swing is the dorsal horn, and the lower part is the ventral horn. The gray matter between the dorsaland ventral horns is calledthe intermediatezone. Everythingelse is white matter, consistingof columns of axonsthat run up and down the spinal cord. Thus, the bundles of axons running along the dorsal surfaceof the cord are called the dorsalcolumns, the bundles of axons lateral to the spinal gray matter on each side are calledthe lateralcolumns, and the bundles on the ventral surface are called t}:.eventral columns. Spinal Cord Structure-Function Relationships. As a generalrule, dorsal horn cellsreceive sensory inputs from the dorsal root fibers,ventral horn cellsproject axonsinto the ventral roots that innervate muscles,and intermediate zone cells are interneurons that shapemotor outputs in response to sensoryinputs and descendingcommands from the brain. ry UNDERSTANDTNGcNssrRUcruRETHRoucH DEVELopMENT l9 |

FIGURE7.I9 Forebrain Difrerentiation of the spinal cord. The butter{ly-shapedcore of the spinalcord is gray matter:drvisible nto dorsal and ventralhorns, Midbrain and an intermediatezone. Surrounding the gray matter are white mattercolumns running rostrocaudally up and down the cord,The Hindbrain narrowCSF-fllled channel is the spinalcanal, (Drawings are not to scare.)

Differentiation

Dorsalhorn Spinal lntermediate gray r--_JL_--- zone matter \./vt Ventralhorn

The large dorsalcolumn contains axons that carry somaticsensory (touch) information up the spinal cord toward the brain. It's like a superhighway that speedsinformation from the ipsilateral side of the body up to nuclei in the medulla. The postsynapticneurons in the medulla give rise to axons that decussateand ascend to the thalamus on the contralateral side. This crossingof axons in the medulla explains why touching the left side of the body is sensedby the right side of the brain. The lateral column contains the axons of the descending corticospinal tract, which also cross {rom one side to the other in the medulla. These axons innervate the neurons of the intermediate zone and ventral horn and communicate the signalsthat 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).

Putting the PiecesTogether

We have discussedthe development of different parts of the CNS: the telencephalon, diencephalon, midbrain, hindbrain, and spinal cord. Now let's put all the individual piecestogether to make a whole central nervous system. Figure 7.20 is a highly schematic illustration that captures the basic or- ganizationalplan 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 diencenhalon.

'^ il:::;.::tr 1'J1" ;;:" .92 cHAPTER7 THE STRUCTUREOFTHE NERVOUSSYSTEM

Rostral Caudal Basal telencephalon Mesencephalon Thalamus (midbrain) Cerebellum Tectum I

Hypothalamus Tegmentum (b) + (a) Forebrain

Cerebral aqueduct

FIGURE7.20 The brainship enterprise. (a)The basicplan of the mammalian brain,with the majorsubdivisions indicated. (b) Majorstructures withineach division of the brain,Note that the telencephaloncon- sistsof two hemispheres,although only one is illustrated.(c)The (c) Thirdventricle Fourthventricle ventricularsvstem.

Surrounding this ventricle are the thalamus and the hypothalamus.The third ventricle is coninuouswith the cerebralaqueduct. Dosal to the aqueduct is the tectum. Ventralto the aqueductis the midbrain tegmentum.The aqueduct connectswith 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. You should seeby now that finding your way around the brain is easyif you can identify which parts of the ventricular system are in the neighbor- hood (Table7.3). Even in the complicatedhuman brain, the ventricular system holds the key to understanding brain structure.

Special Features of the Human CNS So far, we've explored the basicplan of the CNS as it appliesto all mammals. Figure 7.21 comparesthe brains of the rat and the human. You can

COMPONENT RELATEDBMIN STRUCTURES

Latcral Yentricles Cerebral cortex Basaltelencephalon Third ventricle Thalamus Hypothalamus Cerobral aqueduct Tectum Midbralntegmentum Fourth ventricle Cerebellum Pons Medulla V UNDERSTANDINGCNS STRUCTURE THROUGH DEVELOPMENT r93

l.i

Telencephalon

Cerebellum

I l:.1 Diencephalon I I Midbrain Pons (b)

(c)

FIGURE7.2I The rat brain and human brain compared. (a) Dorsalview. (b) Midsagittalview. (c) Lateralview. (Brains are not drawnto the samescale.) see immediately that there are indeed many similarities, but also some obvious differences. Let's start by reviewing the similarities. The dorsal view of both brains reveals the paired hemispheres of the telencephalon (Figure 7 .2Ia\. A midsagittal view ol the two brains shows the telencephalon extending rostrally 194 CHAPTER 7 . THESTRUCTUREOFTHENERVOUSSYSTEM

from the diencephalon (Figure 7.2lbl. 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 swellsbelow the cerebellum,and how structurally elaboratethe cerebellumis. Now let's considersome of the structuraldifferences between the rat and human brains. Figure 7.2Ia revealsa striking one: the many convolutions on the surfaceof the human cerebrum.The groovesin the surfaceof 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 surfaceof the cerebrum is the cerebral cortex. Sulci and gyri result from the tremendousexpansion of the surfacearea of the cerebral cortex during human fetal development.The adult human cortex,measuring about I100 cm2,must fold and wrinkle to fit within the confinesof the skull. This increasein corticalsurface area is one of the "distortions"of the human brain. Clinical and experimentalevidence indicates that the cortex is the seat of uniquely human reasoningand cognition. Without cerebral cortex, a personwould be blind, deaf, mute, and unable to initiate voluntary movement. We will take a closerlook at the structure of the cerebral cortex in a moment. The side views of the rat and human brains in Figure 7.2lc reveal further differencesin the forebrain. One is the small sizeof the olfactorybulb in the human relative to the rat. On the other hand, notice again the growth of the cerebralhemisphere in the human. See how the cerebral hemisphereof the human brain arcs posteriorly,ventrolaterally, and then anteriorly to resemblea ram's horn. The tip of the "horn" Iies right under the temporalbone (temple)of the skull, so this portion of the brain is called the temporal lobe. Three other lobes (named after skull bones) also de- scribethe parts of human cerebrum.The portion of the cerebrumlying just under the frontal bone of the foreheadis calledthe 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 cerebrumunder the occipitalbone, lies the occipital lobe lFigure 7.22).

Central sulcus Parietal lobe Frontal lobe

Occipital Temporallobe lobe FIGURE7.22 The lobes of the human cerebrum. V A GUIDETOTHECEREBML CORTEX t95

FIGURE7.23 The human ventricularsystem. Although the ventriclesare distorted by the growthof the brain,thebasic relationships of the ventriclesto the surroundingbrain are the sameas thoseillustrated in Figure 7.20c..

It is important to realize that, despite the disproportionate growth of the cerebrum,the human brain still follows the basicmammalian 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 (Figure7.23).

V A GUIDETO THE CEREBRALCORTEX Consideringits prominence in the human brain, the cerebralcortex deserves further description. As we will see repeatedly in subsequentchapters, the systemsin the brain that govern the processingof sensations,perceptions, voluntary movement, learning, speech,and cognition all converge in this remarkable organ.

Types of Cerebral Cortex Cerebral cortex in the brain of all vertebrate animals has several common features, as shown in Figure 7.24. 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 closestto the surface (the most superficial cell layer) is separatedfrom 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 apicaldendrttug that extend up to layer I, where they form multiple branches. Thus, we can say that the cerebral cortex has a characteristiccytoarchitec- ture that distinguishesit, for example, from the nuclei of the basal telencephalon or the thalamus. 196 cHAprER 7 . THEsrRUcruREoFTHE NERVoussysrEM

FIGURE7.24 Rat General features of the cerebrd cottex. On the left is the structureof cortex in an alligator;on the right a rat. ln both species,the cortex liesjust under the pia matterof the cerebralhemisphere, containsa molecularlayer: and haspyramidal cellsarranged in layers.

Layer

Figure 7.25 shows a Nissl-stainedcoronal 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 pecu- liar shape. This structure is called the hlppocampus, which, despite its bends, has only a single cell layer. (The term is from the Greek for "sea- horse.") Connected to the hippocampus ventrally and laterally is another type of cortex that has only two cell layers. It is called the olfactory cortex, becauseit is continuous with the olfactory bulb, which sits farther anterior. The olfactory cortex is separatedby a sulcus, called the rhinal ftssure, from another more elaborate type of cortex that has many cell layers. This remaining cortex is called neocortex. Unlike the hippocampus and olfactory cortex, neocortexis 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 neuroscientistsare such neocortical chauvin- ists (ourselvesinduded) that the term cortex, if left unqualified, is usually intended to refer to the cerebral neocortex. A GUIDETOTHECEREBML CORTEX 197

Rhinalfissure

Olfactory bulb

Neocortex Lateral ventricle

Rhinal fissure Olfactory cortex

FIGURE7.25 Three types of cortex in a mammal. In this sectionof a rat brain,the lateralventricles lie betweenthe neocortexand the hippocampuson eachside.The ventricles are not obvr- ousbecause they are very longand thin in thisregion. Below the telencephalonlies the brainstem.What region of brainstem is this, based on the appearanceof the fluid-fllled sDaceat its core?

In Chapter 8, we will discuss the olfactory cortex in the context of the senseof smell. Further discussion of the hippocampus is reserved until later in this book, when we will explore its role in the limbic system (Chapter I8) and in memory and learning (Chapters 24 and 25). The neocortex will figure prominently in our discussionsof vision, audition, somatic sensation, and the control of voluntary movement in Part II, so let's examine its structure in more detail.

Areas of Neocortex Just as cytoarchitecturecan be usedto distinguishthe cerebralcortex from the basaltelencephalon, and the neocortexfrom the olfactorycortex, 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 7.261 . ln this map, each area of cortex having a common cytoarchitecture is given a number. Thus, we have "area 17" al the tip of the occipitallobe, "area 4" just anterior to the central sulcusin the frontal lobe, and so on. What Brodmann guessed,but could not show, was that cortical areasthat look different perform different functions. We now have evidencethat this is t98 CHAPTER 7 . THESTRUCTUREOFTHENERVOUSSYSTEM

FIGURE7.26 Brodmann'scytoarchitectural map of the human cerebralcortex.

true. For instance,we can saythat arca17 is visualcortex because it receives signalsfrom a nucleus of the thalamus that is connectedto the retina at the back of the eye. Indeed, without area t7, a human is blind. Similarly, we can say that area4 is motor cortex, becauseneurons in this area project axons directly to the motor neurons of the ventral horn that command musclesto contract.Notice that the different functions of these two areas are specifiedby their different connections.

Neocortical Evolution and Structure-Function Relationships. A problem that has fascinatedneuroscientists since the time of Brodmann is how neocortexhas changedover the courseof mammalian evolution. The brain is a soft tissue,so there is not a fossilrecord of the cortex of our early mammalian ancestors.Nonetheless, considerable insight can be gainedby comparingthe cortex of different living species(see Figure 7.1). The surface area of the cortex variestremendously among species;for example,a comparisonof mouse, monkey, and human cortex revealsdifferences in size on the order of I:100:1000. On the other hand, there is little differ- ence in the thicknessof the neocortex in different mammals, varying by no more than a factor of two. Thus, we can concludethat the amount of cortex has changed over the course of evolution, but not in its basic structure. Brodmann proposedthat neocortex expandedby the insertion of new areas.Leah Krubitzer at the University of California,Davis, has addressed this issueby studying the structure and function of different cortical areas in many different species(Box 7.5). Her researchsuggests that the pri- mordial neocortex consistedmainly of three types of cortex-cortex that also existsto some degreein all living species.The first type consistsol primary sensoryareas, w}:rich are first to receive signalsfrom the ascendingsen- sory pathways.For example,area 17 is designatedas primary visual cortex, or Vl, becauseit receivesinput lrom the eyesvia a direct path: retina to thalamusto cortex. The secondtype of neocortexconsists of. secondary sensoryareas, so designatedbecause of their heavy interconnectionswith the primary sensory areas. The third type of cortex consistsof motorareas, which are intimately involved with the control of voluntary movement. Thesecortical areasreceive inputs lrom thalamic nuclei that relay information from the basal telencephalonand the cerebellum,and they send CONCLUDINGREMARKS 199

Somatic Visual

Visual

Oltactory Auditory Auditory bulb Human Cat Rat FIGURE7.27 A lateralview of the cerebralcortex in three species.Notice the expansion ofthe humancortex that is neither strictly primary sensory nor strictly motot:

outputs to motor control neurons in the brain stem and spinal cord. For example,because cortical arca 4 sendsoutputs directly to motor neurons in the ventral horn of the spinalcord, it is designatedprimary motor cortex, or Mt. Iftubitzer's analysissuggests that the common mammalian ancestor had on the order of about 20 different areasthat could be assignedto these three categories. Figure 7.27 shows views of the brain of a rat, a cat, and a human, with the primary sensoryand motor areasidentified. It is plain to seethat when we speakof the expansionof the cortex in mammalian evolution, what has expandedis the region that lies in between these areas.Research by Jon "in- Kaasat VanderbiltUniversity and others has shown that much of the between" cortex reflects expansion of the number of secondarysensory areasdevoted to the analysisof sensoryinformation. For example,in pri- matesthat dependheavily on vision, such as humans, the number of secondary visual areashas been estimatedto be between 20 and 40. However, even after we have assignedprimary sensory,motor, and secondarysensory functions to large regions of cortex, a considerableamount of area remainsin the human brain, particularlyin the frontal and temporal lobes. Theseare the associationareas of cortex.Association cortex is a more recent development,a noteworthy characteristicof the primate brain. The emer- gence of the "mind"-our unique ability to interpret behavior (our own and that of others) in terms of unobservablemental states,such as desires, intentions, and beliefs-correlates best with the expansionof the frontal cortex. Indeed, as we will see in Chapter 18, lesionsof the frontal cortex can profoundly alter an individual'spersonality.

V CONCLUDING REMARKS Although we have covereda lot of new ground in this chapter,we have only scratchedthe surfaceof neuroanatomy.Clearly, the brain deservesits statusas the most complex piece of matter in the universe.What we have presentedhere is a shell, or scaffold,of the nervous systemand some of its contents. Understandingneuroanatomy is necessaryfor understandinghow the brain works. This statementis iust as true for an undergraduatefirst-time neurosciencestudent as it is for a neurologistor a neurosurgeon.In fact, 200 CHAPTER7 THESTRUCTURE OFTHE NERVOUS SYSTEM

Evolution of My Brain

by Leah l(rubitzer

How doesevolution build a complexbrain? How did some good fortune, at Vanderbilt University I met Jon Kaas,one mammals,like humans,come to possesa brain with so many of the forerunners in studiesof brain evolution in primates. parts?Can I make one myselfl Sincethat day,my life has never been the same.I had finally Let me assureyou, this mad scientistdid not hatch found somethingthat inspiredme. lt was in Jon'slaboratory from an egg into a fully formed intellectualwith questions that I learned to critically think about how the neocortex in hand.My journey is probablynot unlikeyour own. My might work and to interpret data in light of brain evolution. direction was basedon decisionsmade with little or no in- I immersed myself in the brain and allowed my thinking formation, on taking roads that were somewhat off the about evolution to become completelyintertwined with beaten path and, most importantly,on a burning desire to my thoughts on every aspectof life,both scientificand per- find somethingI could be passionateabout, somethingI sonal.Science consumed me, and it was glorious.During could create,something that would help me make senseof this time, I also had a glimmerof an ideathat there were the world. underlyingprinciples of brain construction that dictated I attended PennsylvaniaState Universityas an under- how brains were made.While I did not know what these graduate,a decisionbased primarily on the fact that I liked rules were, I was convincedthat in order to understand their football team. Like most undergraduates,I was faced them, one must considerthe brain from an evolutionary with the dilemma of decidingwhat I was going to do with perspective.lronically, however, scientists who worked on the rest of my life.My initial decision,prompted by meeting brain evolution were becoming increasinglyrare by 1988. someone I thought was interesting at a wedding,after New technologiessuch as single unit recordingsin awake having consumed severalglasses of champagne,was to monkeyswere all the rage in systemsneuroscience, and major in speechpathology. By the time I realizedthat I was thesetypes of techniques,and the questionsthey addressed, not a clinicalsort of girl,that it was ridiculousto evencon- seemed to eclipsethe comparativeapproach to under- siderhelping others utter coherentsentences when I could standingbrain evolution.As a result,most neuroscientists barely do the same myself,and that I was simply nor pre- were not particularlyinterested in how brains evolved. pared to wear pantyhoseevery day for the rest of my life, Shocking,but true. it was too late. Upon graduation,although I did not know I pulled my head out of the clouds for a brief period exactly what I wanted to do, I was sure I did not want to and accepteda post-doctoral position at MIT to polish my be a speechpathologist. pedigreewith some cutting-edgetechnology. I was at the I decidedto attend graduateschool, mainly to postpone top of the heap,had quite a few publicationsfor a new grad- havingto makethe next big decisionabout my future.Tomy uate student,had the world on a string-and was com-

neuroanatomyhas taken on a new relevancewith the advent ()f methocls ot imaging the living brain (Figure7.28\. An IllustratedGuide to Human Neuroanatomy appearsas an appendix to this chapter.Use the Guide as an atlas to locate various structuresoI interest. Labeling exercisesare 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 Chapter 7 and its appendix will come alive, as we explore how the brain goes about the tasks of smelling, seeing,hearing, sensingtouch, and moving. CONCLUDING REMARKS 201

pletelymiserable. Although I knew this was a path I should follow for all of the obvious reasons,my heart wasn't in it. I madea major decision.I surrenderedmy positionat MII followed my heart, and moved to Australia so that I could work on monotremes,such as the duck-billedplatypus (FigureA) and spiny anteater.My reasoningwas that if I wanted to study how the mammalianneocortex became really complex,the placeto start was with the brain of an animalthat divergedvery earlyin mammalianevolution and still retainedreptilian characteristics, such as egg-laying.I thought that perhapsthe monotreme neocortex would better reflect that of the ancestralneocortex of all mammals, and I could havea better starting point for understanding how a basicplan was modified in different lineages. It was there,in collaborationwith Mike Calfordand Jack Pettigew,that I really came to understandthe evolution of the neocortex at a much deeper level.We worked on a number of amazingmammals, including monotremes, mar- supials,and even large megachirpteranbats. I beganto have an appreciationfor the whole animal and its behaviors, rather than just the brain.ln my mind,this work was critically important, and I spent far greater than an allotted two-year post-doc period in Australia.I remainedthere for more than 6 years. Around 1994,the Australiangovernment changed, and it became increasinglydifficult to get funding to study brain FIGUREA evolution.Luckily, a new Center for Neuroscienceat the A duck-billedplatypus. Universityof California,Davis, had an openingfor an evolutionary neurobiologist.| flew to Davis,gave a talk, and got the job.At U.C. Davis(1995 to the present),we beganin moleculardevelopmental neurobiology have led to a resur- earnestto test our theories of cortical evolution by manip- genceof interest in brain evolution.Our goal is to mimic the ulatingthe nervous system in developinganimals, in an at- evolutionaryprocess to make new cortical areas,and then tempt to apply the rules of brain construction I envisioned to determine how these changesresult in alterationsin be- from my work in Australia.Fortunately, recent advancesin havior.This is a tall order,but a girl hasgot to havea dream.

Gross Organization of the midline(p. 170) coronal plane (p. | 70) Mammalian Nervous System medial(p. 170) central nervous system (CNS) (p. anterior (p. 168) lateral (p. | 70) l7l) >(t rostral(p. 168) ipsilateral(p. 170) brain(p. | 7l) UJE posterior (p. 168) contralateral(p. | 70) spinalcord (p. l7l) Yd. caudal(p. 168) midsagittalplane (p. 170) cerebrum(p. l7l) trJ dorsal(p. 168) sagittalplane (p. 170) cerebralhemispheres (p. l7l) F ventral (p. | 68) horizontalplane (p. 170) cerebellum(p. l7l) CHAPTER 7 . THESTRUCTUREOFTHENERVOUSSYSTEM

FIGURE7.28 MRI scansof the authors.How manystructures can you abe? S CONCLUDINGREMARKS 203

brainstem (p. l7l) locus(p. 180) corpuscallosum (p. l8a) spinalnerve (p.172) ganglion(p. 180) internalcapsule (p. l8a) dorsafroot (p.172) nerve(p. 180) tectum(p. 187) ventralroot (p. 172) white mafter(p. 180) tegmentum(p. 187) peripheralnervous system (PNS) tract (p. 180) cerebralaqueduct (p. 187) (p. 172) bundle(p. 180) pons(p. 188) somaticPNS (p. 172) capsule(p. 180) medullaoblongata (medulla) dorsalroot ganglion(p. 173) commissure(p. 180) (p. 188) visceralPNS (p. 173) lemniscus(p. 180) fourth ventricle(p. 188) autonomicnervous system (ANS) neuraltube (p. l8l) spinalcanal (p. 190) (p.173) neuralcrest (p. 18l) dorsalhorn (p. 190) afferent(p. | 73) neurulation(p. l8l) ventralhorn (p. 190) efferent(p. | 73) differentiation(p. 182) sulcus(p. 194) cranialnerve (p. | 73) forebrain(p. 183) gyrus(p. 194) meninges(p. 173) midbrain(p. 183) temporallobe (p. 194) duramater (p. 173) hindbrain(p. 183) frontallobe (p. 194) arachnoidmembrane (p. 173) diencephalon(p. l8a) centralsulcus (p. 194) piamater (p. l7a) telencephalon(p. 184) parietallobe (p. 194) cerebrospinalfluid (CSF)(p. 174\ olfactorybulb (p. 184) occipitallobe (p. 194) ventricular system (p. l7a) lateralventricle (p. 184) thirdventricle (p. 184) A Guide to the Cerebral Understanding CNS Structure cerebralcortex (p. l8a) Cortex Through Development basaltelencephalon (p. l8a) hippocampus(p. 196) graymatter (p. 180) thalamus(p. l8a) olfactorycortex (p. 196) cortex (p. 180) hypothalamus(p. l8a) neocortex(p. 196) nucleus(p. 180) corticalwhite matter(p. l8a) cytoarchitecturalmap (p. 197) substantia(p. 180)

l. Are the dorsalroot gangliain the centralor peripheralnervous system? 2. ls the myelinsheath of optic nerve axonsprovided by Schwanncells or oligodendroglia?Why? > (,/) you are a neurosurgeon,about to removea tumor lodgeddeep insidethe brain.Thetop of the '-&J 3. lmaginethat z skull hasbeen removed.Whatnow lies betweenyou and the brainlWhich layer(s)must be cut beforeyou -o reachthe CSF? neural tube? Neural crest? ul l- 4. What is the fate of tissue derived from the embryonic &Q.t 5. Name the three main parts of the hindbrain.Whichof theseare also part of the brain steml IJJ f 6. Where is CSFproduced?What path does it take before it is absorbedinto the bloodstreamlName the parts O of the CNS it will passthrough in its voyagefrom brain to blood. 7. What are three featuresthat characterizethe structure of cerebral cortex? CHAPTER 7 . THESTRUCTUREOFTHENERVOUSSYSTEM