Table Of ContentFUNDAMENTAL
NEUROSCIENCE
Fourth Edition
FUNDAMENTAL
NEUROSCIENCE
FOURTH EDITION
Edited by
L R. S
ARRY QUIRE
VA Medical Center San Diego, California
University of California, San Diego, La Jolla, California
D B
ARWIN ERG
University of California, San Diego
La Jolla, California
F E. B
LOYD LOOM
The Scripps Research Institute
La Jolla, California
S L
ASCHA DU AC
The Salk Institute
La Jolla, California
A G
NIRVAN HOSH
University of California, San Diego
La Jolla, California
N C. S
ICHOLAS PITZER
University of California, San Diego
La Jolla, California
AMSTERDAM(cid:129)BOSTON(cid:129)HEIDELBERG(cid:129)LONDON
NEWYORK(cid:129)OXFORD(cid:129)PARIS(cid:129)SANDIEGO
SANFRANCISCO(cid:129)SINGAPORE(cid:129)SYDNEY(cid:129)TOKYO
AcademicPressisanimprintofElsevier
AcademicPressisanimprintofElsevier
225WymanStreet, Waltham,MA02451, USA
The Boulevard,LangfordLane,Kidlington, Oxford,OX51GB,UK
©2013Elsevier Inc.Allrights reserved.
Nopartofthispublicationmaybereproducedortransmitted inanyformorbyanymeans,electronic ormechanical,
includingphotocopying, recording, oranyinformationstorageandretrieval system,without permissioninwritingfrom
thePublisher.Detailsonhow toseekpermission,further informationaboutthePublisher’spermissionspoliciesand our
arrangementswithorganizationssuchastheCopyrightClearanceCenterandtheCopyright LicensingAgency,canbe
foundatourwebsite:www.elsevier.com/permissions.
Thisbookand theindividualcontributions contained initareprotected undercopyright bythePublisher (other than
asmaybenotedherein).
Notices
Knowledgeandbestpracticeinthisfieldareconstantlychanging.Asnewresearchandexperiencebroadenour
understanding,changesinresearchmethods,professionalpractices,ormedicaltreatmentmaybecomenecessary.
Practitionersand researchers mustalwaysrelyontheir ownexperienceand knowledgeinevaluatingandusing any
information,methods,compounds, orexperiments describedherein. Inusingsuchinformationormethodsthey
shouldbemindful oftheirown safetyand thesafetyofothers,including partiesforwhomtheyhaveaprofessional
responsibility.
Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors,assumeanyliabilityforany
injuryand/ordamagetopersonsorpropertyasamatterofproductsliability,negligenceorotherwise,orfromanyuseor
operationofanymethods,products,instructions,orideascontainedinthematerialherein.
LibraryofCongressCataloging-in-Publication Data
Fundamentalneuroscience /editedbyLarrySquire ...[etal.].–4thed.
p.cm.
Includesbibliographicalreferencesand index.
ISBN978-0-12-385870-2(alk.paper)
1.Neurosciences. I.Squire,LarryR.
QP355.2.F8622012
612.8–dc23 2012020285
BritishLibraryCataloguing-in-PublicationData
AcataloguerecordforthisbookisavailablefromtheBritishLibrary.
CoverImage:Theconfocalimageshowsdopaminergic (green)andGABAergic (red)neurons inthedevelopingXenopus
accessoryolfactory bulbthatmediatekinshiprecognitionamongsiblings. Thenumberofdopaminergic andGABAergic
neurons changesin responsetosustained exposuretoolfactorystimuli. CourtesyofDavideDulcisandNicholasSpitzer.
ForinformationonallAcademicPresspublications
visitourwebsite:http://store.elsevier.com
Printedin China
1213141516 10987654321
List of Boxes
2.1: The Neuron Doctrine 16
2.2: Cajal: Iconoclast to Icon 20
2.3: Anatomical Relationships in the Vertebrate Body 21
5.1: Nernst Equation 96
5.2: Goldman-Hodgkin-Katz Equation 98
5.3: Voltage-Clamp Technique 103
5.4: Ion Channels and Disease 107
6.1: MAO and COMT Inhibitors in the Treatment of Neuropsychiatric Disorders 125
6.2: Going for Gases as Neurotransmitter 134
10.1: Optogenetics 213
11.1: Neuronal Cable Theory and Computational Modeling 232
11.2: Dendritic Recording 235
11.3: Imaging Dendritic Function 242
12.1: Positron Emission Tomography (PET) and Functional Magnetic Resonance Imaging (fMRI) 266
12.2: HepaticEncephalopathy 275
14.1: Neural Stem Cells 318
15.1: Adult Neurogenesis 352
17.1: Torpedo Electric Organ 386
17.2: Synaptic Targets in Neurodevelopmental Disorders 398
19.1: α–Bungarotoxin 448
20.1: Rho GTPases Control the Structure of the Dendritic Cytoskeleton 464
21.1: Sensitive Periods in Humans 480
21.2: Filial Imprinting: Babies Learn to Recognize Their Parents 492
23.1: Identifying a Genetic Locus Linked to Bitter Taste Perception 516
23.2: Taste Cells in Fruit Flies 518
23.3: Sensing Thousands of Chemicals with a Handful of Neurons 522
25.1: Otoacoustic Emissions 560
25.2: Cochlear Implants 561
25.3: Giant Synaptic Terminals: Endbulbs and Calyces 568
25.4: Bat Echolocation 573
26.1: Kuffler’sStudyofCenter-SurroundRetinalGanglionCells 578
26.2: Quantitative Methods in the Study of Visual Neurons Classification of Retinal Ganglion Cells 582
26.3: Inherited and Acquired Defects of Color Vision: Retinal and Cortical Mechanisms 584
26.4: Vision in Mice 585
27.1: Central Pattern Generator Networks 604
28.1: Species Diversity in Neuromuscular Systems 614
28.2: Myasthenia and Myasthenic Disorders 618
28.3: Motor Neuron Diseases 622
28.4: Nonlinear Properties of Motor Neurons and CPG Interneurons 625
28.5: Neural Control of Human Walking 627
29.1: Vestibular Plasticity 637
29.2: Meniere Syndrome 638
29.3: Pyramids in the Brain 640
xv
xvi
LISTOFBOXES
29.4: Motor Neuroprosthetics 648
30.1: Parkinson’s Disease 657
30.2: The MPTP Story 667
30.3: Ventral System of the Basal Ganglia 670
30.4: Huntington’s Disease 671
30.5: Deep Brain Stimulation 671
30.6: Obsessive-Compulsive Disorder 672
30.7: Tourette Syndrome 673
30.8: The Role of the Subthalamic Nucleus in Stopping 674
31.1: Parasagittal Stripes: The Basis of Cerebellar Microcircuits? 680
31.2: Differences Between the Vestibular and NonVestibular Portions of the Cerebellum 682
31.3: Clinical Testing Can Reveal Cerebellar Damage 688
31.4: Cognition, Emotion, and the Cerebellum 690
32.1: Eye Movements and Reading 700
32.2: Eye Movement Disorders 708
34.1: Autonomic Postganglionic Neurons Can Change Their Transmitter Phenotypes 739
34.2: AutonomicReflexes:ActivatedbyVisceralAfferents,AutonomicAfferents,orJustAfferents? 740
34.3: DiseasesandAgingImpairtheAutonomicWisdomoftheBody 744
34.4: CentralANSCircuitsIntegrateAutonomicReflexeswithAffectiveorEmotionalResponses 745
35.1: Experimental Analysis of Ventilation 751
35.2: CNSLesionsProduceAbnormalBreathingPatterns 753
35.3: Why Two Distinct Oscillators? 755
35.4: Cardiovascular Disease 760
35.5: DisordersofBreathingAreWidespreadandSerious 763
36.1: Validating Satiation Factors 771
36.2: The Glucostatic Hypothesis 773
36.3: Treatment of Obesity 774
37.1: Water Channels 786
37.2: Diabetes Insipidus 788
37.3: Water Intoxication 791
37.4: Salt Appetite After Adrenocortical Dysfunction 794
37.5: Thirst and Salt Appetite During Hypovolemia in Rats 796
38.1: Historical Perspective on Hypothalamic Hormones 800
38.2: Endocrine-Disrupting Chemicals and Their Effects on Neuroendocrine Systems 816
39.1: Neuronal Control of Drosophila Circadian Behavior 823
39.2: Molecular Mechanisms of Circadian Timekeeping in Drosophila 826
39.3: Circadian-Based Sleep Disorders, Clock Genes and Neuropsychiatric Diseases 829
39.4: Chronopharmacology 838
39.5: Jet Lag and Shift Work 840
39.6: Lost Without a Clock 842
41.1: Logic of Methodology Used in Behavioral Neuroscience 874
41.2: Separation of Sensory and Response Factors in the Dopaminergic Syndrome of Neglect 876
41.3: Psychophysics of Hedonism as Measured by Brain Stimulation Reward 878
41.4: Impulsivity and Compulsivity 883
41.5: OPIOID Receptors 885
41.6: Allostasis 891
41.7: Craving 891
41.8: Major Depressive Disorders 894
42.1: How Do We Learn About Brain Evolution? 902
42.2: Why Brain Size Is Important 910
43.1: The Optical Fractionator Stereological Method 931
43.2: Dyslexia 935
43.3: Triplet Repeat Disorders 936
xvii
LISTOFBOXES
44.1: Case Study of Associative Agnosia 949
44.2: The Issue of Viewpoint Dependence in Object Recognition 955
44.3: Linking Category-Selective Regions into Specialized Networks 963
45.1: Area 7a Neurons Carry Object-Centered Signals in a Constructional Task 978
47.1: Is Memory More than Changes in Synaptic Strength? 1020
48.1: Alzheimer’s Disease 1032
50.1: Functional Topography 1076
50.2: Attention Deficit Hyperactivity Disorder 1080
Preface to the Fourth Edition
In this fourth edition of Fundamental Neuroscience, we including critical periods. The fourth and fifth sections
have tried to improve on the third edition with a (SensorySystemsandMotorSystems)describetheneural
volume that effectively introduces students to the full organization of each sensory modality and the organiza-
range of contemporary neuroscience. Neuroscience is a tion of the brain pathways and systems important for
large field founded on the premise that all of behavior locomotion, voluntary action, and eye movements. The
and all of mental life have their origin in the structure sixth section (Regulatory Systems) describes the variety
and function of the nervous system. Today, the need of hypothalamic and extra-hypothalamic systems that
for a single-volume introduction to neuroscience is support motivation, reward, and internal regulation,
greater than ever. Toward the end of the twentieth cen- including respiration, food and water intake, neuro-
tury, the study of the brain moved from a peripheral endocrine function, circadian rhythms, and sleep and
position within both the biological and psychological dreaming. The final section (Behavioral and Cognitive
sciences to become an interdisciplinary field that is Neuroscience) describes the neural foundations of the
now central within each discipline. The maturation of so-called higher mental functions, including percep-
neuroscience has meant that individuals from diverse tion, attention, memory, language, spatial cognition, and
backgrounds—includingmolecularbiologists,computer executive function. Additional chapters cover human
scientists, and psychologists—are interested in learning brain evolution, cognitive development and aging, and
about the structure and function of the brain and about consciousness.Thechapterscontainmorethan100Boxes
how the brain works. In addition, new techniques and that describe clinical conditions, techniques, and special
tools have become available to study the brain in topics related to chapter content. The volume is also
increasingdetail.Newgeneticmethodshavebeenintro- accompanied by companion websites for students and
duced to delete or overexpress single genes with spatial instructors, which present all the Figures and Boxes. In
andtemporalspecificity.Neuroimagingtechniquessuch addition, the instructor’s website includes sample test
as functional magnetic resonance imaging (fMRI) have questionsfor eachchapter thatdrawattention tothe key
been developed that allow study of the living human factsandconceptsinthechapters.
brain while it is engaged in cognition. The authors of the chapters and boxes are working
This fourth edition attempts to capture the promise scientists,expertsinthetopicstheycover.TheEditorsedi-
and excitement of this fast-moving discipline. All the ted the chapters to achieve consistency of style and con-
chapters have been rewritten and updated. Thevolume tent.AtAcademicPress/Elsevier Science, theprojectwas
begins with an opening chapter that provides an over- coordinatedbyMicaHaley(AcquisitionsEditor),andwe
viewofthediscipline.Asecondchapterpresentsfunda- aregratefultoherforherleadershipandadvicethrough-
mentalinformation about thearchitectureandanatomy out the project. In addition, April Graham (Editorial
of nervous systems. The remainder of the volume Project Manager) very capably and efficiently supervised
(Sections II–VII) presents the major topics of neu- the development of the book, and Lisa Lamenzo (Project
roscience. The second section (Cellular and Molecular Manager)expertlycoordinateditsproduction.
Neuroscience)considersthecellularandsubcellularorga- The Editors of Fundamental Neuroscience hope that
nization of neurons, the physiology of nerve cells, and users of this book, and especially the students who will
howsignalingoccursbetweenneurons.Thethirdsection become the next generation of neuroscientists, find the
(Nervous System Development) includes discussion subject matter of neuroscience as interesting and excit-
of neural induction, cell fate, migration, pathfinding, ing as we do.
synapseformation,programmedcelldeath,synapseelim-
ination, development of dendrites, and early experience, The Editors
xix
About the Editors
LarryR.SquireisDistinguishedProfessorofPsychia- Sascha du Lac is an Investigator of the Howard
try, Neurosciences, and Psychology at the University of Hughes Medical Institute and an Associate Professor of
California School of Medicine, San Diego, and Research SystemsNeurobiologyattheSalkInstituteforBiological
Career Scientist at the Veterans Affairs Medical Center, Studies. Her research focuses on the cellular machinery
San Diego. He investigates the organization and neuro- and circuit mechanisms that mediate cerebellar learning
logicalfoundationsofmemory.HeisaformerPresident in the sense of balance.
of the Society for Neuroscience and is a member of
the National Academy of Sciences and the Institute of Anirvan Ghosh is Stephen Kuffler Professor in the
Medicine. Division of Biological Sciences at the University of
California, San Diego. His research interests include
Darwin K. Berg is Distinguished Professor and Chair the development of synaptic connections in the central
ofNeurobiologyintheDivisionofBiologicalSciencesat nervous system and the role of activity-dependent gene
the University of California, San Diego. He has served expression in cortical development. He is recipient of
as Chair of the Biology Department and Councilor of the Presidential Early Career Award for Scientists and
the Society for Neuroscience. He currently is Treasurer Engineers, the Society for Neuroscience Young Investi-
for the Society and a Board member of the Kavli Insti- gator Award, and the UCSD Revelle College Outstand-
tute for Brain and Mind. His research is focused on the ing Faculty Award.
roles of nicotinic cholinergic signaling in the vertebrate
nervous system. Nicholas C. Spitzer is Distinguished Professor in the
Division of Biological Sciences at the University of
Floyd E. Bloom is Professor Emeritus in the Molecu- California, San Diego. His research is focused on the
lar and Integrative Neuroscience Department (MIND) role of electrical activity in neuronal differentiation. He
at The Scripps Research Institute. His recent awards has been chairman of the Biology Department and the
includetheSarnatAwardfromtheInstituteofMedicine Neurobiology Section,a trusteeofthe Grass Foundation,
and the Salmon Medal of the New York Academy of and served as Councilor of the Society for Neuroscience.
Medicine. He is a former President of the Society for He is a member of the American Academy of Arts and
NeuroscienceandisamemberoftheNationalAcademy Sciences, Co-Director of the Kavli Institute for Brain and
of Sciences and the Institute of Medicine. MindandEditor-in-ChiefofBrainFacts.org.
xxi
Contributors
IgorAllaman EcolePolytechnique FédéraledeLausanne, JacquelineP.Gottlieb ColumbiaUniversity Collegeof
Lausanne,Switzerland Physiciansand Surgeons,NewYork,NY
JocelyneBachevalier EmoryUniversity, Atlanta,GA JamesL. Gould Princeton University,Princeton, NJ
MarthaW.Bagnall Northwestern University, Chicago,IL MartynGoulding TheSalk Institute,LaJolla,CA
JamesF.Baker Northwestern University, Chicago,IL StenGrillner Karolinska Institute,Stockholm,Sweden
AndrewH.Bell MRCCognitionand BrainSciencesUnit, WilliamA.Harris CambridgeUniversity, Cambridge,
Cambridge,UK UnitedKingdom
FloydE.Bloom TheScrippsResearchInstitute,LaJolla,CA VolkerHartenstein University ofCaliforniaat LosAngeles,
ScottT.Brady UniversityofIllinoisatChicago,Chicago,IL LosAngeles,CA
MarianneBronner CaliforniaInstitute ofTechnology, MaryE.Hatten Rockefeller University,NewYork, NY
Pasadena,CA MichaelHäusser UniversityCollegeLondon,London,
PeterBrophy UniversityofEdinburgh,Edinburgh,Scotland UnitedKingdom
M.ChristianBrown HarvardMedicalSchool,Boston,MA StewartH.Hendry JohnsHopkinsUniversity,Baltimore,MD
ElizabethA.Buffalo EmoryUniversity SchoolofMedicine, J.AllanHobson HarvardMedicalSchool,DivisionofSleep,
Atlanta,GA Boston, MA
StevenJ.Burden NYUMedicalCenter, NewYork,NY PatrickR.Hof Mount SinaiSchoolofMedicine,
NewYork,NY
JohnH.Byrne UniversityofTexasMedicalSchoolatHouston,
Houston,TX StevenS.Hsiao JohnsHopkinsUniversity,Baltimore, MD
DavidN.Caplan HarvardMedicalSchool, Boston,MA Yuh-NungJan HowardHughesMedicalInstitute,University
ofCaliforniaatSanFrancisco,SanFrancisco,CA
J.Patrick Card University ofPittsburgh,Pittsburgh,PA
JonH.Kaas VanderbiltUniversity, Nashville,TN
HollisCline The Scripps ResearchInstitute, LaJolla, CA
SabineKastner PrincetonUniversity, Princeton,NJ
CarolL.Colby University ofPittsburgh,Pittsburgh,PA
DavidR.Colman (Deceased.) Formerlyat Montreal GrahameKidd TheCleveland ClinicFoundation,
NeurologicalInstitute, Montreal,Quebec,Canada Cleveland,OH
JeandeVellis University ofCaliforniaatLosAngeles, ClemensKiecker King’sCollege London,London,
LosAngeles,CA UnitedKingdom
JavierDeFelipe CajalInstitute,Madrid,Spain EricI.Knudsen StanfordUniversity SchoolofMedicine,
Stanford,CA
ArielY.Deutch VanderbiltUniversity SchoolofMedicine,
Nashville,TN ChristofKoch CaliforniaInstitute ofTechnology,Pasadena,
CAandAllenInstitute forBrainScience,Seattle,WA
SaschaduLac TheSalk Institute,LaJolla,CA
AlexL.Kolodkin JohnsHopkinsUniversity Schoolof
GregoryElder The MountSinaiSchool ofMedicineand
Medicine,Baltimore, MD
JamesJ.PetersVAMedicalCenter, Bronx,NY
GeorgeF.Koob TheScrippsResearchInstitute,LaJolla,CA
PatrickEmery University ofMassachusetts MedicalSchool,
Worcester,MA RichardKrauzlis National EyeInstitute,Bethesda, MD;
TheSalkInstitute forBiological Studies,LaJolla,CA
BarryJ.Everitt University ofCambridge,Cambridge,
UnitedKingdom JeffLichtman HarvardUniversity,Cambridge,MA
JackL.Feldman University ofCaliforniaat LosAngeles, AndrewLumsden King’sCollegeLondon,London,
DavidGeffenSchoolofMedicine,Los Angeles,CA UnitedKingdom
MiguelA.GamaSosa Mount SinaiSchoolofMedicine, PierreJ.Magistretti Ecole PolytechniqueFédéralede
NewYork,NY Lausanne,Lausanne, Switzerland;University of
LausanneandCHUV,Lausanne, Switzerland
AnirvanGhosh University ofCaliforniaatSanDiego,
LaJolla, CA JosephR.Manns EmoryUniversity,Atlanta,GA
AndreaC.Gore TheUniversityofTexasatAustin,Austin,TX MichaelMauk UniversityofTexas atAustin, Austin,TX
xxiii
xxiv
CONTRIBUTORS
DavidA.McCormick YaleUniversity SchoolofMedicine, MarcH.Schieber University ofRochester, Rochester,NY
New Haven,CT HowardSchulman AllosterosTherapeutics,Sunnyvale,CA
DonaldR.McCrimmon Northwestern University, ThomasL. Schwarz Children’sHospital,Boston,MA
Chicago, IL
KristinScott University ofCaliforniaatBerkeley,
GeorgeZ.Mentis CenterforMotorNeuronBiologyand Berkeley,CA
Disease, ColumbiaUniversity,New York,NY
NelsonSpruston HHMIJaneliaFarmResearch Campus,
EarlK.Miller Massachusetts Institute ofTechnology, Ashburn,VA
Cambridge,MA
EdwardM.Stricker UniversityofPittsburgh,Pittsburgh,PA
CarolanneE.Milligan WakeForestSchoolofMedicine,
GregStuart AustralianNational University,Canberra,
Winston-Salem, NC
Australia
JohnathanW.Mink University ofRochester Medical LarryW.Swanson University ofSouthernCalifornia,
Center, Rochester, NY LosAngeles,CA
ShaunF.Morrison OregonHealth andScienceUniversity, JuanC.Tapia ColumbiaUniversity,New York,NY
Portland,OR
MarcTessier-Lavigne TheRockefellerUniversity,NewYork,
CarlR.Olson CarnegieMellonUniversity,Pittsburgh,PA NY
RonaldW.Oppenheim WakeForestSchoolofMedicine, RogerB.H.Tootell AthinoulaA.MartinosCenterfor
Winston-Salem, NC Biomedical Imaging, Charlestown, MA; Harvard Medical
Edward F. Pace-Schott Harvard Medical School, School,Boston,MA
Boston, MA; Massachusetts General Hospital, BruceD.Trapp TheCleveland ClinicFoundation,
Charlestown, MA Cleveland,OH
LuizPessoa University ofMaryland,College Park,MD LeslieG.Ungerleider National Institute ofMentalHealth,
Bethesda,MD
TerryL.Powley Purdue University,West Lafayette,IN
W.MartinUsrey CenterforNeuroscience,Universityof
ToddM.Preuss EmoryUniversity,Atlanta,GA
CaliforniaDavis,Davis,CA
PeterR.Rapp NationalInstitute onAging,Baltimore, MD
JosephG.Verbalis GeorgetownUniversity,Washington,DC
R.ClayReid HarvardMedicalSchool,Boston, MA;
ChristopherS.vonBartheld University ofNevadaSchool
AllenInstitute forBrainScience, Seattle,WA
ofMedicine, Reno,NV
JohnH.Reynolds TheSalk Institute,LaJolla,CA
JonathanD.Wallis UniversityofCaliforniaat Berkeley,
TrevorW.Robbins UniversityofCambridge,Cambridge, Berkeley,CA
UnitedKingdom
M.NealWaxham UniversityofTexasMedical Schoolat
JoshSanes HarvardUniversity, Cambridge,MA Houston,Houston, TX
JosephSantos-Sacchi YaleUniversity SchoolofMedicine, DavidR.Weaver University ofMassachusetts Medical
New Haven,CT School,Worcester, MA
PeterScheiffele BiozentrumoftheUniversity ofBasel, StephenC.Woods UniversityofCincinnatiMedicalCenter,
Basel,Switzerland Cincinnati,OH
