NEUROSCIENCEExploring the Brai n

Second Edition

MARK F . BEAR,

BARRY W. CONNORS

MICHAEL A. PARADISO

Preface / vi i

Acknowledgments / xii i

PART I

FOUNDATION S

Chapter 1

Introduction to Neuroscience / 2

Chapter 2

Neurons and Gila / 22

Chapter 3

The Neuronal Membrane at Rest / 50

Chapter 4

The Action Potential / 73

Chapter 5

Synaptic Transmission / 98

Chapter 6

Neurotransmitter Systems / 130

Chapter 7

The Structure of the Nervous System / 163

PART II

SENSORY AND MOTOR SYSTEM S

Chapter 8

The Chemical Senses / 254

Chapter 9

The Eye / 280

Chapter 10 The Central Visual System / 313

Chapter 11 The Auditory and Vestibular Systems / 349

Chapter 12 The Somatic Sensory System / 396

Chapter 13 Spinal Control of Movement/43 6

Chapter 14 Brain Control of Movement / 465

PART III

THE BRAIN AND BEHAVIO R

Chapter 15 Chemical Control of the Brain and Behavior / 496

Chapter 16 Motivation / 522

Chapter 17 Sex and the Brain / 547

Chapter 18 Brain Mechanisms of Emotion / 580

Chapter 19 Rhythms of the Brain / 606

Chapter 20 Language and Attention / 637

Chapter 21

Mental Illness / 675

PART IV

THE CHANGING BRAI N

Chapter 22 Wiring the Brain / 704

Chapter 23 Memory Systems / 739

Chapter 24 Molecular Mechanisms of Learning and Memory / 775

Glossary / 809

References and Suggested Readings / 83 1

Index / 843

x ~ . PART I FOUNDATIONS

Rough Endoplasmic Reticulum / 29Smooth Endoplasmic Reticulum and the Golgi

Chapter 1

Apparatus / 3 1Introduction to Neuroscience The Mitochondrion / 3 1

INTRODUCTION / 3

The Neuronal Membrane / 32The Cytoskeleton / 32

THE ORIGINS OF NEUROSCIENCE / 3

Microtubules / 33Views of the Brain in Ancient Greece / 4

n Box 2 .2 Of Special Interest: Alzheimer' sViews of the Brain During the Roman Empire / 4

Disease and the Neuronal Cytoskeleton / 34Views of the Brain From the Renaissance to the

Microfilaments / 33Nineteenth Century / 5

Neurofilaments / 36Nineteenth-Century Views of the Brain / 7

The Axon / 36Nerves as Wires / 7

The Axon Terminal / 37Localization of Specific Functions to Different Parts

The Synapse / 38of the Brain / 10

Axoplasmic Transport / 38The Evolution of Nervous Systems / 11

n Box 2.3 Of Special Interest: Hitching a RideThe Neuron : The Basic Functional Unit of the Brain /

on "Retrorail" / 4 112

Dendrites / 39NEUROSCIENCE TODAY / 13

n Box 2 .4 Of Special Interest: Menta lLevels of Analysis / 13

Retardation and Dendritic Spines / 42Molecular Neuroscience / 13

n Box 2 .5 Path of Discovery: The Story ofCellular Neuroscience / 13

Dendritic Protein Synthesis, by Oswal dSystems Neuroscience / 13

Steward / 44Behavioral Neuroscience / 13

CLASSIFYING NEURONS / 40Cognitive Neuroscience / 14

Classification Based on the Number of Neurites / 40Neuroscientists / 14

Classification Based on Dendrites / 40The Scientific Process / 15

Classification Based on Connections / 40Observation / 15

Classification Based on Axon Length / 41Replication / 15

Classification Based on Neurotransmitter / 42Interpretation / 15

GLIA / 42Verification / 16

Astrocytes / 43The Use of Animals in Neuroscience Research / 16

Myelinating Glia / 44The Animals / 16

Other Non-Neuronal Cells / 47Animal Welfare / 17

CONCLUDING REMARKS / 47Animal Rights / 17

`Q" KEY TERMS / 48The Cost of Ignorance : Nervous System Disorders / 18

3 REVIEW QUESTIONS / 49CONCLUDING REMARKS / 203 REVIEW QUESTIONS / 21

Chapter 3The Neuronal Membrane at Rest

Chapter 2

INTRODUCTION / 5 1Neurons and GliaTHE CAST OF CHEMICALS / 52

INTRODUCTION / 23

Cytosol and Extracellular Fluid / 52THE NEURON DOCTRINE / 23

Water / 52The Golgi Stain / 24

Ions / 52Cajal's Contribution / 25

The Phospholipid Membrane / 53n Box 2 .1 Of Special Interest: Advances in

The Phospholipid Bilayer / 54Microscopy / 27

Protein / 54THE PROTOTYPICAL NEURON / 26

Protein Structure / 54The Soma / 26

Channel Proteins / 57The Nucleus / 26

Ion Pumps / 57

THE MOVEMENT OF IONS / 58

n Box 4.5 Of Special Interest: Multiple Sclerosis,Diffusion / 58

a Demyelinating Disease 194n Box 3 .1 Brain Food: A Review of Moles and ACTION POTENTIALS, AXONS, AND DENDRITES / 94

Molarity / 59

n Box 4.6 Of Special Interest: The Eclecti cElectricity / 58

Electric Behavior of Neurons / 96THE IONIC BASIS OF THE RESTING MEMBRANE

CONCLUDING REMARKS / 97POTENTIAL / 60

'4 KEY TERMS / 97Equilibrium Potentials / 60

3 REVIEW QUESTIONS / 97The Nernst Equation / 62n Box 3.2 Brain Food : The Nernst Equation / 64 Chapter 5

The Distribution of Ions Across the Membrane / 63

Synaptic TransmissionRelative Ion Permeabilities of the Membrane at Rest / 63

INTRODUCTION / 99n Box 3 .3 Brain Food : The Goldman

n Box 5 .1 Of Special Interest: Otto Loewi andEquation ! 66

Vagusstoff / 100The Wide World of Potassium Channels / 65

TYPES OF SYNAPSES / 100n Box 3 .4 Path of Discovery: Shaker Flies and

Electrical Synapses / 100Their Defective Potassium Channels, by Lily

Chemical Synapses / 10 1and Yuh Nung Jan / 67

CNS Synapses / 102The Importance of Regulating the External Potassium

The Neuromuscular Junction / 103Concentration / 69

PRINCIPLES OF CHEMICAL SYNAPTIC TRANSMISSION / 105n Box 3 .5 Of Special Interest: Death by Lethal

Neurotransmitters / 105Injection / 71

Neurotransmitter Synthesis and Storage / 107CONCLUDING REMARKS / 71

Neurotransmitter Release / 109Q` KEY TERMS / 72

n Box 5 .2 Path of Discovery : The Functiona l3 REVIEW QUESTIONS / 72

Anatomy of Neurotransmitter Release, b y

Chapter 4

Thomas Südhof / 11 0

The Action Potential 10 Box 5 .3 Brain Food: How to SNARE a

Vesicle / 11 1INTRODUCTION / 74

Neurotransmitter Receptors and Effectors / 11 2PROPERTIES OF THE ACTION POTENTIAL / 74

Transmitter-Gated Ion Channels / 11 2The Ups and Downs of an Action Potential / 74

n Box 5 .4 Brain Food : Reversal Potentials / 114

n Box 4 .1 Brain Food : Methods of Recording G-Protein-Coupled Receptors / 11 3Action Potentials / 75

Autoreceptors / 11 6The Generation of an Action Potential / 74

Neurotransmitter Recovery and Degradation / 11 6The Generation of Multiple Action Potentials / 76

Neuropharmacology / 117THE ACTION POTENTIAL IN THEORY / 78

n Box 5 .5 Of Special Interest: Bacteria, Spiders ,

Membrane Currents and Conductances l 78

Snakes, and You / 11 8

The Ins and Outs of an Action Potential / 80

PRINCIPLES OF SYNAPTIC INTEGRATION / 11 9

THE ACTION POTENTIAL IN REALITY / 80

The Integration of EPSPs / 11 9

The Voltage-Gated Sodium Channel / 82

Quantal Analysis of EPSPs / 11 9

Sodium Channel Structure / 82

EPSP Summation / 120

Functional Properties of the Sodium Channel 1 84

The Contribution of Dendritic Properties to Synapti c

n Box 4 .2 Brain Food: The Patch-Clamp Integration / 120

Method / 85

Dendritic Cable Properties / 120

n Box 4 .3 Path of Discovery: The Challenge of Excitable Dendrites / 122

Resolving Voltage-Gated Channels, by Erwin

Inhibition / 123

Neher / 86

n Box 5 .6 Of Special Interest: Startling

The Effects of Toxins on the Sodium Channel / 87

Mutations / 124

Voltage-Gated Potassium Channels / 88

IPSPs and Shunting Inhibition / 123

Putting the Pieces Together / 89

The Geometry of Excitatory and Inhibitory

ACTION POTENTIAL CONDUCTION / 89

Synapses / 125

Factors Influencing Conduction Velocity / 91

Modulation / 126

n Box 4 .4 Of Special Interest: Local CONCLUDING REMARKS / 127

Anesthesia / 93

'Q$ KEY TERMS / 128

Myelin and Saltatory Conduction / 92

3 REVIEW QUESTIONS / 129

Chapter 6

Anatomical References / 164Neurotransmitter Systems The Central Nervous System / 167

INTRODUCTION / 131

The Cerebrum / 167

STUDYING NEUROTRANSMITTER SYSTEMS / 132

The Cerebellum / 167

Localization of Transmitters and Transmitter

The Brain Stem / 167The Spinal Cord / 168Synthesizing Enzymes / 132

The Peripheral Nervous System / 169Immunocytochemistry / 132In Situ Hybridization / 133

The Somatic PNS / 169

Studying Transmitter Release / 135

The Visceral PNS / 169

Studying Synaptic Mimicry / 136

Afferent and Efferent Axons / 169

Studying Receptors / 136

The Cranial Nerves / 170

Neuropharmacological Analysis / 136

The Meninges / 170

Ligand-Binding Methods / 137

The Ventricular System / 170n Box 6 .1 Path of Discovery: A Brief History of n Box 7 .1 Of Special Interest: Water on the

the Nicotinic Receptor, by Jean-Pierre

Brain / 17 2Changeux / 139

Imaging the Living Brain / 173Molecular Analysis / 140

Computed Tomography / 173NEUROTRANSMITTER CHEMISTRY / 140

Magnetic Resonance Imaging / 173Cholinergic Neurons / 141

n Box 7 .2 Brain Food : Magnetic Resonancen Box 6 .2 Brain Food: Pumping Ions and Imaging / 17 4

Transmitters / 142

Functional Brain Imaging / 173Catecholaminergic Neurons / 143

n Box 7 .3 Brain Food: Functional Imaging o fSerotonergic Neurons / 145

Brain Activity : PET and fMRI / 176Amino Acidergic Neurons / 145

UNDERSTANDING CNS STRUCTURE THROUG HOther Neurotransmitter Candidates and Intercellular

DEVELOPMENT / 175Messengers / 146

Formation of the Neural Tube / 175n Box 6 .3 Of Special Interest: Are Cannabinoids I• Box 7 .4 Of Special Interest: Nutrition and the

Neurotransmitters? / 148TRANSMITTER-GATED CHANNELS / 147

Neural Tube / 180

The Basic Structure of Transmitter-Gated

Three Primary Brain Vesicles / 178

Channels / 147

Differentiation of the Forebrain / 179

Amino Acid Gated Channels / 150

Differentiation of the Telencephalon an d

Glutamate-Gated Channels / 150

Diencephalon / 179

n Box 6 .4 Of Special Interest: The Brain's

Forebrain Structure-Function Relationships / 184

Exciting Poisons / 152

Differentiation of the Midbrain / 185

GABA-Gated and Glycine-Gated Channels / 151

Midbrain Structure-Function Relationships / 185

G-PROTEIN-COUPLED RECEPTORS AND EFFECTORS / 153

Differentiation of the Hindbrain / 186The Basic Structure of G-Protein-Coupled

Hindbrain Structure-Function Relationships / 186Receptors / 153

Differentiation of the Spinal Cord / 188The Ubiquitous G-Proteins / 154

Spinal Cord Structure-Functio nG-Protein-Coupled Effector Systems / 156

Relationships / 188The Shortcut Pathway / 156

Putting the Pieces Together / 189Second Messenger Cascades / 156

Special Features of the Human CNS / 19 1Phosphorylation and Dephosphorylation / 158

A GUIDE TO THE CEREBRAL CORTEX / 193The Function of Signal Cascades / 159

Types of Cerebral Cortex / 194DIVERGENCE AND CONVERGENCE IN NEUROTRANSMITTER

Areas of Neocortex / 195SYSTEMS / 160

Neocortical Evolution and Structure-FunctionCONCLUDING REMARKS / 161

Relationships / 196V KEY TERMS / 161

n Box 7 .5 Path of ; ;scovery: Evolution of th e3 REVIEW QUESTIONS / 162

Evolution of the Neocortex,

Chapter 7

by Jon Kaas / 19 7

The Structure of the Nervous System CONCLUDING REMARKS / 199'Q KEY TERMS / 200

INTRODUCTION / 164

3 REVIEW QUESTIONS / 20 1GROSS ORGANIZATION OF THE MAMMALIAN NERVOUS

APPENDIX : ILLUSTRATED GUIDE TO HUMA NSYSTEM / 164

NEU ROANATOMY / 202

PART II SENSORY AND MOTOR SYSTEMS

The Pupillary Light Reflex / 289The Visual Field / 289

Chapter 8

Visual Acuity / 289The Chemical Senses MICROSCOPIC ANATOMY OF THE RETINA / 290

INTRODUCTION / 255

The Laminar Organization of the Retina / 292

TASTE / 255

Photoreceptor Structure / 292

The Basic Tastes / 256

Regional Differences in Retinal Structure / 293

The Organs of Taste / 256

PHOTOTRANSDUCTION / 294

Taste Receptor Cells / 258

Phototransduction in Rods / 294

Mechanisms of Taste Transduction / 258

Phototransduction in Cones / 297

Saltiness / 258

n Box 9.4 Path of Discovery: Genes and Vision ,

Sourness / 261

by Jeremy Nathans 1300

Sweetness / 261

Color Detection / 299

Bitterness / 261

n Box 9 .5 Of Special Interest: Genetic Mistake sAmino Acids / 261

and the Colors We See / 302Central Taste Pathways / 263

Dark and Light Adaptation / 300n Box 8 .1 Of Special Interest: Memories of a RETINAL PROCESSING / 300

Very Bad Meal 1265

Transformations in the Outer Plexiform Layer / 302The Neural Coding of Taste / 263

Bipolar Cell Receptive Fields / 303SMELL / 267

RETINAL OUTPUT / 304n Box 8 .2 Of Special Interest: Human Ganglion Cell Receptive Fields / 304

Pheromones? / 266

Types of Ganglion Cells / 307The Organs of Smell / 268

Color-Opponent Ganglion Cells / 307n Box 8 .3 Path of Discovery: Tales of Two Parallel Processing / 31 0

Species: Hormones, Pheromones, and

CONCLUDING REMARKS / 31 0Behavior, by Martha McClintock / 268

=Q` KEY TERMS / 31 1Olfactory Receptor Neurons / 269

3 REVIEW QUESTIONS / 312Olfactory Transduction / 270

Central Olfactory Pathways / 273

Chapter 10Spatial and Temporal Representations of Olfactory

The Central Visual SystemInformation / 276

Olfactory Population Coding / 277

INTRODUCTION / 314

Olfactory Maps / 277

THE RETINOFUGAL PROJECTION / 314

Temporal Coding in the Olfactory System / 278

The Optic Nerve, Optic Chiasm, and Optic Tract / 31 5

CONCLUDING REMARKS / 278

Right and Left Visual Hemifields / 31 5

V KEY TERMS / 279

Targets of the Optic Tract / 31 7

3 REVIEW QUESTIONS / 279

n Box 10 .1 Of Special Interest: David andGoliath 1 319

Chapter 9

Nonthalamic Targets of the Optic Tract / 31 8

The Eye Retinotopy / 319

INTRODUCTION / 281

THE LATERAL GENICULATE NUCLEUS / 32 1

PROPERTIES OF LIGHT / 282

The Segregation of Input by Eye and Ganglion Cel l

Light / 282

Type / 32 1

Optics / 282

Receptive Fields / 323

THE STRUCTURE OF THE EYE / 283

Nonretinal Inputs to the LGN / 323

Gross Anatomy of the Eye / 283

ANATOMY OF THE STRIATE CORTEX / 324

Ophthalmoscopic Appearance of the Eye / 284

Lamination of the Striate Cortex / 325

n Box 9 .1 Of Special Interest : Demonstrating The Cells of Different Layers / 325

the Blind Regions of Your Eye / 285

Input-Output Organization of Different

Cross-Sectional Anatomy of the Eye / 285

Layers / 326

n Box 9.2 Of Special Interest : Eye LGN Input to Layer IVC / 326

Disorders / 287

Innervation of Other Cortical Layers / 327

IMAGE FORMATION BY THE EYE / 286

Blobs / 328

Refraction by the Cornea / 286

Parallel Pathways / 329

Accommodation by the Lens / 288

PHYSIOLOGY OF THE STRIATE CORTEX / 330

n Box 9 .3 Of Special Interest . Vision Correction The M Channel / 330

With Lenses and Surgery / 290

The P-IB Channel / 332

Orientation Columns / 333

MECHANISMS OF SOUND LOCALIZATION / 374n Box 10 .2 Brain Food: Optical Imaging of

Localization of Sound in the Horizontal Plane / 374Neural Activity / 334

The Sensitivity of Binaural Neurons to Soun dPhysiology of the Blobs / 336

Location / 375Putting the Pieces Together / 336

n Box 11 .3 Brain Food: Auditory Neurons, FastBEYOND STRIATE CORTEX / 337

and Sure / 378The Dorsal Stream / 339

Localization of Sound in the Vertical Plane / 378Area MT / 339

n Box 11 .4 Path of Discovery: A Searci i for th en Box 10 .3 Path of Discovery: Seeking the Impossible, by Masakazu Konishi / 380

Brain's Representation of Coherent Motion,

AUDITORY CORTEX / 380by Anthony Movshon / 340

Neuronal Response Properties / 38 1Dorsal Areas and Motion Processing / 339

n Box 11 .5 Of Special Interest: How Doe sThe Ventral Stream / 342

Auditory Cortex Work? Consult aArea V4 / 342

Specialist / 382Area IT / 342

The Effects of Auditory Cortical Lesions an dFROM SINGLE NEURONS TO PERCEPTION / 342

Ablation / 383n Box 10 .4 Of Special Interest : Deptli n Box 11 o Of Special Interest : Auditory

Perception, Random Dots, and the

Disorders / 384Shopping Mall / 344

THE VESTIBULAR SYSTEM / 385From Photoreceptors to Grandmother Cells / 343

The Vestibular Labyrinth / 385Parallel Processing / 343

The Otolith Organs / 386CONCLUDING REMARKS / 347

The Semicircular Canals / 388,0 KEY TERMS / 347

Central Vestibular Pathways and Vestibula r3 REVIEW QUESTIONS / 348

Reflexes / 389The Vestibulo-ocular Reflex (VOR) / 39 1

Chapter 11

Vestibular Pathology / 393The Auditory and Vestibular Systems CONCLUDING REMARKS / 393

INTRODUCTION / 351

KEY TERMS / 394

THE NATURE OF SOUND / 351

6, REVIEW QUESTIONS / 395

n Box 1 1 .1 Of Special Interest : Ir, end / 353THE STRUCTURE OF THE AUDITORY SYSTEM / 353

Chapter 1 2

THE MIDDLE EAR / 355

The Somatic Sensory System

Components of the Middle Ear / 355

INTRODUCTION / 397Sound Force Amplification by the Ossicles / 356

TOUCH / 397The Attenuation Reflex / 356

Mechanoreceptors of the Skin / 398THE INNER EAR / 357

Vibration and the Pacinian Corpuscle / 400Anatomy of the Cochlea / 357

Two-Point Discrimination / 40 1Physiology of the Cochlea / 359

Primary Afferent Axons / 402The Response of the Basilar Membrane to

The Spinal Cord / 403Sound / 359

Segmental Organization of the Spinal Cord / 403The Organ of Corti and Associated Structures / 359

n Box 12 .1 Of Special interest: Herpes ,Transduction by Hair Cells / 362

Shingles, and Dermatomes / 408The Innervation of Hair Cells / 365

Sensory Organization of the Spinal Cord / 407Amplification by Outer Hair Cells / 366

The Dorsal Column-Medial Lemniscal Pathway / 407n Box 11 .2 Of Special Interest: Ni Ears : n Box 12 .2 Brain Food : Lateral Inhibition / 41 1

Otoacoustic Emissions / 367

The Trigeminal Touch Pathway / 41 0CENTRAL AUDITORY PROCESSES / 368

Somatosensory Cortex / 41 0The Anatomy of Auditory Pathways / 368

Primary Somatosensory Cortex / 410Response Properties of Neurons in the Auditory

Cortical Somatotopy / 413Pathway / 370

Cortical Map Plasticity / 41 6ENCODING SOUND INTENSITY AND FREQUENCY / 371

n Box 12 .3 Path of Discovery: The Power o fStimulus Intensity / 371

Mutable Maps, by Michae l ^'erzenich / 418Stimulus Frequency, Tonotopy, and Phase

The Posterior Parietal Cortex / 420Locking / 372

PAIN / 42 1Tonotopy / 372

n Box 12 .4 Of Special Interest: The Misery ofPhase Locking / 372

Life Without Pain / 422

Nociceptors and the Transduction of Painful

n Box 13 .4 Path of Discovery : Locomotion :Stimuli / 422

From Molecules to Networks and Behavior ,Types of Nociceptors / 423

by Sten Grillner / 46 1Hyperalgesia / 423

CONCLUDING REMARKS / 463Primary Afferents and Spinal Mechanisms / 424

KEY TERMS / 463Ascending Pain Pathways / 426

3 REVIEW QUESTIONS / 464

The Spinothalamic Pain Pathway / 426The Trigeminal Pain Pathway / 427

Chapter 14

The Thalamus and Cortex / 427

Brain Control of Movement

The Regulation of Pain / 428

INTRODUCTION / 466Afferent Regulation / 430

DESCENDING SPINAL TRACTS / 467Descending Regulation / 430

The Lateral Pathways / 468The Endogenous Opioids / 431

The Effects of Lateral Pathway Lesions / 469n Box 12.5 Of Special Interest : Pain and the

The Ventromedial Pathways 1470Placebo Effect / 432

The Vestibulospinal Tracts / 470TEMPERATURE / 432

The Tectospinal Tract / 47 1Thermoreceptors / 432

The Pontine and Medullary Reticulospina lThe Temperature Pathway / 434

Tracts / 47 1CONCLUDING REMARKS / 434

THE PLANNING OF MOVEMENT BY THE CEREBRA LV KEY TERMS / 435

CORTEX / 4733 REVIEW QUESTIONS / 435

Motor Cortex / 473The Contributions of Posterior Parietal and Prefronta l

Chapter 13

Cortex / 474

Spinal Control of Movement Neuronal Correlates of Motor Planning / 475n Box 14 .1 Of Special Interest : Behaviora l

INTRODUCTION / 437

Neurophysiology / 476THE SOMATIC MOTOR SYSTEM / 437

THE BASAL GANGLIA / 477THE LOWER MOTOR NEURON / 439

Anatomy of the Basal Ganglia / 478The Segmental Organization of Lower Motor

The Motor Loop / 479Neurons / 439

Basal Ganglia Disorders / 479Alpha Motor Neurons / 440

n Box 14 .2 Of Special Interest: Do NeuronsGraded Control of Muscle Contraction by Alpha

in Diseased Basal Ganglia Commi tMotor Neurons / 440

Suicide? / 480Inputs to Alpha Motor Neurons / 442

THE INITIATION OF MOVEMENT BY PRIMARY MOTO RTypes of Motor Units / 442

CORTEX / 482

Neuromuscular Matchmaking / 443

The Input-Output Organization of M1 / 483

n Box 13 .1 Of Special Interest: Amyotrophic

The Coding of Movement in M1 / 483

Lateral Sclerosis / 445

n Box 14 .3 Path of Discovery: Distributed

EXCITATION-CONTRACTION COUPLING / 444

Coding in the Superior Colliculus, by Jame s

n Box 13 .2 Of Special Interest :

asthenia

T . Mcllwain / 486

Gravis /446

The Malleable Motor Map / 484

Muscle Fiber Structure / 445

THE CEREBELLUM / 487n Box 14 .4 .)f Special Interest: Involuntary

The Molecular Basis of Muscle Contraction / 446

Movements, Normal and Abnormal / 488n Box 13 .3 Of Special lntere' Ducher.

Anatomy of the Cerebellum / 489Muscular Dystrophy / 452

The Motor Loop Through the Lateral Cerebellum / 490SPINAL CONTROL OF MOTOR UNITS / 449

Programming the Cerebellum / 492Proprioception From Muscle Spindles / 449

CONCLUDING REMARKS / 492The Myotatic Reflex / 450

w, KEY TERMS / 493Gamma Motor Neurons / 453

3 REVIEW QUESTIONS / 493Proprioception From Golgi Tendon Organs / 454

Proprioception From the Joints / 457Spinal Interneurons / 457

PART III THE BRAIN AND BEHAVIORInhibitory Input / 457

Chapter 1 5Excitatory Input / 458

Chemical Control of the Brain and Behavior The Generation of Spinal Motor Programs fo rWalking / 459

INTRODUCTION / 497

THE SECRETORY HYPOTHALAMUS / 499

The Effects of Decreased Leptin Levels on th eAn Overview of the Hypothalamus / 499

Hypothalamus / 530Homeostasis / 500

The Control of Feeding by Lateral HypothalamicStructure and Connections of the

Peptides / 53 1Hypothalamus / 500

THE SHORT-TERM REGULATION OF FEEDIN GPathways to the Pituitary / 500

BEHAVIOR / 534Hypothalamic Control of the Posterior

Eating, Digestion, and Satiety / 53 5Pituitary / 501

Gastric Distension / 536Hypothalamic Control of the Anterior

Cholecystokinin / 536Pituitary / 502

Insulin / 536® Box 15 .1 Of Special Interest: Stress and the

II Box 16 .2 Of Special Interest: DiabetesBrain / 506

Mellitus and Insulin Shock / 538THE AUTONOMIC NERVOUS SYSTEM / 505

WHY DO WE EAT? / 539ANS Circuits / 507

The Role of Dopamine in Motivation / 539Sympathetic and Parasympathetic Divisions / 507

Box 16 .3 Of Special Interest: Dopamine an dThe Enteric Division / 510

Addiction / 54 1Central Control of the ANS / 510

Serotonin, Food, and Mood / 540Neurotransmitters and the Pharmacology of Autonomic

OTHER MOTIVATED BEHAVIORS / 540Function / 511

Drinking / 542Preganglionic Neurotransmitters / 511

Temperature Regulation / 543Postganglionic Neurotransmitters / 512

CONCLUDING REMARKS / 54 5THE DIFFUSE MODULATORY SYSTEMS OF THE BRAIN / 512

KEY TERMS / 546Anatomy and Functions of the Diffuse Modulatory

3 REVIEW QUESTIONS / 546Systems / 51 3

The Noradrenergic Locus Coeruleus / 513

Chapter 17

Box 15 .2 Path of Discovery: Illuminating

Sex and the Brain

the Catecholamines of the Brain,

INTRODUCTION / 548by Kjell Fuxe J 514

SEX AND GENDER / 548The Serotonergic Raphe Nuclei / 515

The Genetics of Sex / 549The Dopaminergic Substantia Nigra and Ventral

Sexual Reproduction / 550Tegmental Area / 516

Sexual Development and Differentiation / 55 1The Cholinergic Basal Forebrain and Brain Stem

THE HORMONAL CONTROL OF SEX / 552Complexes / 517

The Principal Male and Female Hormones / 553Drugs and the Diffuse Modulatory Systems / 517

The Control of Steroid Sex Hormones by the PituitaryHallucinogens / 518

and Hypothalamus / 554Stimulants / 519

Hormonal Cycles and Feedback to the Brain / 554CONCLUDING REMARKS / 520

THE NEURAL BASIS OF SEX-RELATED BEHAVIORS / 556V` KEY TERMS / 521

Reproductive Organs and Their Control / 5573 REVIEW QUESTIONS / 521

Mammalian Mating Strategies / 559The Neurochemistry of Reproductive Behavior / 560

Chapter 16

WHY AND HOW MALE AND FEMALE BRAINS DIFFER / 562Motivation Sexual Dimorphisms of the Central Nervou sINTRODUCTION / 523

System / 563THE HYPOTHALAMUS, HOMEOSTASIS, AND MOTIVATED

Sexual Dimorphisms of Cognition / 566BEHAVIOR / 523

Sex Hormones, the Brain, and Behavior / 567THE LONG-TERM REGULATION OF FEEDING

n Box 17 .1 Of Special Interest : Bird Songs an dBEHAVIOR / 524

Bird Brains / 570Energy Balance / 524

n Box 17 .2 Of Special Interest: John/Joan an dHormonal and Hypothalamic Regulation of Body Fat

the Basis of Gender Identity / 572and Feeding / 526

The Activational Effects of Estrogens on Dendriti cBody Fat and Food Consumption / 526

Spines / 57 1n Box 16 .1 Path of Discovery: Fat Chance, by

SEXUAL ORIENTATION / 574Jeffrey Friedman / 528

Hypothalamic Nuclei in Heterosexuals an dThe Hypothalamus and Feeding / 527

Homosexuals / 575The Effects of Elevated Leptin Levels on the

Box 17 .3 Path of Discovery: Queer Science, byHypothalamus/ 527

Simon LeVay / 576

A Genetic Basis for Sexual Orientation? / 575

Functions of Brain Rhythms / 61 1

CONCLUDING REMARKS / 577

The Seizures of Epilepsy / 61 3

V' KEY TERMS / 578

SLEEP / 614

3 REVIEW QUESTIONS / 579

The Functional States of the Brain / 614The Sleep Cycle 1616

Chapter 18

n Box 19 .1 Of Special Interest: Walking ,Brain Mechanisms of Emotion Talking, and Screaming in Your Sleep / 61 7

INTRODUCTION / 581

Why Do We Sleep? / 618

WHAT IS EMOTION? 1 581

n Box 19.2 Of Special Interest: The Longest AII -

Theories of Emotion / 581

Nighter / 61 9

The James-Lange Theory / 581

Functions of Dreaming and REM Sleep / 61 9

The Cannon-Bard Theory / 582

Neural Mechanisms of Sleep / 62 1

From Theory to Experimental Studies / 584

Wakefulness and the Ascending Reticula r

THE LIMBIC SYSTEM CONCEPT / 584

Activating System / 62 1

Broca's Limbic Lobe / 584

Falling Asleep and the Non-REM State / 622

The Papez Circuit / 585

Mechanisms of REM Sleep / 622

n Box 18 .1 Of Special Interest : The Amazing n Box 19 .3 Of Special interest : Narcolepsy / 62 5

Case of Phineas Gage 1586

Sleep-Promoting Factors / 624

Difficulties With the Single Emotion System

Gene Expression During Sleeping and Waking / 626

Concept / 588

CIRCADIAN RHYTHMS / 626

FEAR AND ANXIETY / 588

Biological Clocks / 627

The Klüver-Bucy Syndrome / 588

The Suprachiasmatic Nucleus : A Brain Clock / 629

The Amygdala / 589

n Box 19 .4 Of Special Interest: Mutant Hamste r

Anatomy of the Amygdala 1590

Clocks / 632

The Effects of Amygdala Destruction and

SCN Mechanisms / 63 1

Stimulation / 591

n Box 19 .5 Path of Discovery: Clock Genes, by

A Neural Circuit for Learned Fear / 591

Joseph Takahashi / 634

n Box 18 .2 Path of Discovery: Startling CONCLUDING REMARKS / 633

Memories, by Michael Davis / 593

Q KEY TERMS / 636

ANGER AND AGGRESSION / 592

3 REVIEW QUESTIONS / 636

The Hypothalamus and Aggression / 594Sham Rage / 595

Chapter 20

Electrical Stimulation of the Hypothalamus / 595

Language and Attention

The Midbrain and Aggression / 597

INTRODUCTION / 638The Amygdala and Aggression / 597

LANGUAGE AND THE BRAIN / 639Surgery to Reduce Human Aggression / 598

n Box 20.1 Of Special Interest : Is Languag en Box 18 .3 Of Special Interest: The Fronta Unique to Humans? / 638

Lobotomy / 599

The Discovery of Specialized Language Areas in th eSerotonin and Aggression / 598

Brain / 640Serotonin Receptor Knockout Mice / 600

Broca's Area and Wernicke's Area / 640REINFORCEMENT AND REWARD / 600

n Box 20 .2 Of Special Interest: The Wad aElectrical Self-Stimulation and Reinforcement! 601

Procedure / 64 1Brain Stimulation in Humans / 602

Types of Aphasia and Their Causes / 642Dopamine and Reinforcement / 603

n Box 20 .3 Path of Discovery: Foreig nCONCLUDING REMARKS / 604

Accents and Native Tongues, by Sheila E .Q' KEY TERMS / 605

Blumstein / 6443 REVIEW QUESTIONS / 605

Broca's Aphasia / 642

Chapter 19

Wernicke's Aphasia / 645

Rhythms of the Brain Aphasia and the Wernicke-Geschwind Model / 647Conduction Aphasia / 648

INTRODUCTION / 607

Aphasia in Bilinguals and the Deaf / 649THE ELECTROENCEPHALOGRAM / 607

Lessons Learned From Split-Brain Studies / 650Recording Brain Waves / 607

Language Processing in Split-Brain Humans / 65 1EEG Rhythms / 608

Anatomical Asymmetry and Language ! 655Mechanisms and Meanings of Brain Rhythms / 609

Language Studies Using Brain Stimulation and PE TThe Generation of Synchronous Rhythms 1611

Imaging / 656

The Effects of Brain Stimulation on Language/656

Psychotherapy / 692PET Imaging of Language Processing / 657

Antidepressants / 693n Box 20 .4 Of Special Interest : Hearing Sight

Lithium / 693and Seeing Touch / 660

SCHIZOPHRENIA / 694ATTENTION / 659

A Description of Schizophrenia / 695n Box 20 .5 Of Special Interest: Attention-

Biological Bases of Schizophrenia 1695Deficit/Hyperactivity Disorder / 662

Genes and the Environment / 695Behavioral Consequences of Attention / 661

The Dopamine Hypothesis / 696Attention Enhances Detection / 661

The Glutamate Hypothesis / 698Attention Speeds Reaction Times / 664

Treatments for Schizophrenia / 700Neglect Syndrome as an Attentional Disorder / 664

CONCLUDING REMARKS / 700Physiological Effects of Attention / 666

V KEY TERMS / 70 1Functional MRI Imaging of Attention to

3 REVIEW QUESTIONS 170 1Location / 666

PET Imaging of Attention to Features / 666Enhanced Neuronal Responses in Parieta l

Cortex / 669Receptive Field Changes in Area V4 / 670

Chapter 22How Is Attention Directed? / 672

Wiring the BrainCONCLUDING REMARKS / 673

INTRODUCTION / 705V KEY TERMS / 674

THE GENESIS OF NEURONS / 7063 REVIEW QUESTIONS / 674

Cell Proliferation / 706

Chapter 21

1111 Box 22 .1 Of Special Interest: Neurogenesis i nthe Adult ^;eocortex / 708Mental Illness

Cell Migration 1709INTRODUCTION / 676

Cell Differentiation / 71 0MENTAL ILLNESS AND THE BRAIN / 676

Differentiation of Cortical Areas / 71 0Psychosocial Approaches to Mental Illness / 676

THE GENESIS OF CONNECTIONS / 712Biological Approaches to Mental Illness / 678

The Growing Axon / 71 3ANXIETY DISORDERS 1679

Axon Guidance / 71 5A Description of Anxiety Disorders / 679

Guidance Cues / 71 5Panic Disorder 1679

Establishing Topographic Maps / 71 5Agoraphobia / 680

n Box 22.2 Of Special Interest : Why Don' tn Box 21 .1 Of Special Interest: Agoraphobia Axons Regenerate in Our CNS? / 71 8

With Panic Attacks / 681

Synapse Formation / 71 7Obsessive-Compulsive Disorder / 680

THE ELIMINATION OF CELLS AND SYNAPSES / 71 9Biological Bases of Anxiety Disorders / 680

Cell Death / 720The Stress Response / 680

Changes in Synaptic Capacity / 72 1Regulation of the HPA Axis by the Amygdala and

ACTIVITY-DEPENDENT SYNAPTIC REARRANGEMENT / 722Hippocampus / 682

Synaptic Segregation / 723Treatments for Anxiety Disorders / 684

Segregation of Retinal Axons in the LGN / 723Psychotherapy / 684

Segregation of LGN Inputs in the StriateAnxiolytic Medications / 684

Cortex / 725MOOD DISORDERS / 686

n Box 22.3 Path of Discovery : Exploring Visua lA Description of Mood Disorders / 686

Cortical Plasticity, by Torsten Wiesel / 726Depression / 686

n Box 22 .4 Brain Food: The Critical Perio dBipolar Disorder / 687

Concept / 728n Box 21 .2 Of Special Interest: A Magical Synaptic Convergence / 726

Orange Grove in a Nightmare / 688

Synaptic Competition / 729Biological Bases of Mood Disorders / 687

Modulatory Influences / 730The Monoamine Hypothesis / 687

ELEMENTARY MECHANISMS OF CORTICAL SYNAPTICThe Diathesis-Stress Hypothesis / 689

PLASTICITY / 731n Box 21 .3 Path of Discovery: Stress and Mood, Excitatory Synaptic Transmission in the Immature Visua l

by Charles Nemeroff / 691

System / 732Treatments for Mood Disorders / 692

Long-Term Synaptic Potentiation / 734Electroconvulsive Therapy / 692

Long-Term Synaptic Depression / 734

WHY DO CRITICAL PERIODS END? / 736

CONCLUDING REMARKS / 773CONCLUDING REMARKS / 737

V` KEY TERMS / 773V KEY TERMS / 738

3 REVIEW QUESTIONS / 7743 REVIEW QUESTIONS / 738

Chapter 23

Chapter 24

Memory SystemsMolecular Mechanisms of Learning and Memory

INTRODUCTION / 776INTRODUCTION / 740

PROCEDURAL LEARNING / 776TYPES OF MEMORY AND AMNESIA / 740

Declarative and Nondeclarative Memory / 740

Nonassociative Learning / 777

II Box 23 .1 Of Special Interest : An

Habituation / 777

Extraordinary Memory / 742

Sensitization ! 77 7

Long-Term and Short-Term Memory / 741

Associative Learning / 77 7Classical Conditioning / 77 7

Amnesia / 743

Instrumental Conditioning / 778n Box 23 .2 Of Special Interest: Forgettable

Fish / 745

SIMPLE SYSTEMS : INVERTEBRATE MODELS O F

THE SEARCH FOR THE ENGRAM / 745

LEARNING / 779

Lashley's Studies of Maze Learning in Rats / 745

Nonassociative Learning in Aplysia / 779

Hebb and the Cell Assembly / 747

Habituation of the Gill Withdrawal Reflex / 779

II Box 23 .3 Brain Food . A Model of a

Sensitization of the Gill Withdrawal Reflex / 78 1

Distributed Memory / 749

Associative Learning in Aplysia / 783

Localization of Declarative Memories in the

VERTEBRATE MODELS OF LEARNING 1786

Neocortex / 748

Synaptic Plasticity in the Cerebellar Cortex / 786

Studies in Monkeys / 750

Anatomy of the Cerebellar Cortex / 786

Studies in Humans / 751

Long-Term Depression in the Cerebella r

Electrical Stimulation of the Human Temporal

Cortex / 788

Lobes / 751

Mechanisms of Cerebellar LTD / 788

THE TEMPORAL LOBES AND DECLARATIVE MEMORY / 752

Synaptic Plasticity in the Hippocampus an d

The Effects of Temporal Lobectomy / 752

Neocortex / 79 1

A Human Case Study : H . M. / 753

Anatomy of the Hippocampus / 791

n Box 23 .4 Path of Discovery: Discovering

Properties of LTP in CAI / 792

Memory in the Medial Temporal Lobe With

Mechanisms of LTP in CAI / 793

H. M ., by Brenda Milner / 755

n Box 24 .1 Brain Food: Synaptic Plasticity:

The Medial Temporal Lobes and Memory Timing Is Everything 1795

Processing / 754

Long-Term Depression in CAI / 796

An Animal Model of Human Amnesia / 756

LTP, LTD, and Memory / 797

The Diencephalon and Memory Processing / 758

n Box 24 .2 Of Special Interest: Memory

A Human Case Study : N . A . / 759

Mutants / 800

Korsakoff's Syndrome / 760

n Box 24 .3 Path of Discovery: Of Mice and

Memory Functions of the Hippocampus / 760

Memories, by Susumu Tonegawa / 802

The Effects of Hippocampal Lesions in Rats / 760

THE MOLECULAR BASIS OF LONG-TERM MEMORY / 801

Place Cells / 762

Persistently Active Protein Kinases / 80 1

Spatial Memory, Working Memory, and Relational

CaMKII and LTP / 803

Memory / 763

Protein Synthesis / 803THE STRIATUM AND PROCEDURAL MEMORY / 766

Protein Synthesis and MemoryRodent Recordings and Lesions in the Striatum / 766

Consolidation / 803Habit Learning in Humans and Nonhuman

Cyclic AMP Response Element Binding Protein an dPrimates 1 767

Memory / 804THE NEOCORTEX AND WORKING MEMORY / 768

Structural Plasticity and Memory / 805The Prefrontal Cortex and Working Memory / 769

CONCLUDING REMARKS / 806Lateral Intraparietal Cortex (Area LIP) and Working

,9$ KEY TERMS / 806Memory / 771

3 REVIEW QUESTIONS ! 807