Encyclopedia of the Human Brain

3289 Pages·2002·4.73 MB·English

by  V. S. Ramachandran

PREFACE
The functions of the human brain are the last major lookingfornewfieldstoconquer,aclinicianwanting
challengetoscience.Despitehavingmaderapidstrides tobecomeup-to-dateonrecentresearchinhisorher
in understanding the cosmos, subatomic particles, field,orevenaninterestedlayreader.
molecular biology, and genetics, we still know very Eachofthearticleshasbeenthroughalongprocess
little about the organ that made these discoveries of author nomination, peer review, revision, and
possible. How does the activity of 100 billion nerve copyediting. Most of the entries were written by
cellsFmere wisps of protoplasm that constitute the acknowledged experts in the field. Given the nature
brainFgiverisetothebroadspectrumofabilitiesthat and scope of this enterprise, a degree of overlap
wecallconsciousness,mind,andhumannature? among the articles was not only inevitable but also
Thereisnow,morethaneverbefore,arealneedfora desirable,sinceourgoalwastoensurethateacharticle
standard reference source covering all aspects of the wasaself-containedsummaryofonespecificaspectof
humanbrainandnervoussystem,andtheEncyclope- thehumanbrain.Givenspacelimitations,eachauthor
dia of the Human Brain is the most up-to-date and was encouraged to provide a broad overview of an
comprehensivecoveragetodate.Itisacompendiumof areaofresearchratherthananexhaustivereview.The
articles contributed by many of the world’s leading resultisastimulatingandinformativecompilationof
expertsinneuroscienceandpsychology.Theseessays material.
willbeofinteresttoawiderangeofindividualsinthe Theeightiesweredubbedthe‘‘decadeofthebrain,’’
behavioralandhealthsciences. an apt term given the subsequent progress made in
Writteninanengaging,accessiblestyle,theencyclo- understanding the structure, function, and develop-
pedianotonlyisanimportantmajorreferenceworkbut ment of this mysterious organ. This encyclopedia
also can be browsed informally by anyone who seeks should prove to be an invaluable resource on this
answers about the activities and effects of the brain, fascinating subject and would nothavebeen possible
suchaswhyandhowwedream,whatpartsofthebrain without the dedicated efforts of more than 350
areinvolvedinmemory,howwerecognizehumanfaces authors, 12associateeditors,150 peerreviewers, and
and other objects, what are the brain mechanisms thefollowingAcademicPresspersonnel:NikkiLevy,
involved in cognition and language, what causes Barbara Makinster, Christopher Morris, Carolan
phantom limb pain, what are the implications of left- Gladden,JoannaDinsmore,andJocelynLofstrom.
handedness, or what current treatments are available
forParkinson’sdisease.HereintheEncyclopediaofthe
Human Brain will be found brief yet comprehensive
summariesonallofthesetopicsandsome200more. V.S.Ramachandran
Manyofthearticleswillappealequallytoastudent Editor-in-Chief
preparing an essay for class, a novice researcher UniversityofCalifornia,SanDiego
xxxv
Editorial Advisory Board
Antonio R. Damasio
University of Iowa College of Medicine
Antonio R. Damasio, the Van Allen Professor and Head of Neurology at the University of Iowa, and
AdjunctProfessorattheSalkInstitute,hashadamajorinfluenceonourunderstandingoftheneuralbasis
ofdecision-making,emotion,languageandmemory,andconsciousness.Heelucidatescriticalproblemsin
thefundamentalneuroscienceofmindandbehaviorattheleveloflarge-scalesystemsinhumans,although
his investigations have also encompassed parkinsonism and Alzheimer’s disease. The laboratories that he
andHannaDamasio(adistinguishedneurologistwhoisindependentlyrecognizedforherachievementsin
neuroimaging and neuroanatomy) created at the University of Iowa are a leading center for the
investigation of cognition using both the lesion method and functional imaging.
Dr.DamasioisamemberoftheInstituteofMedicineoftheNationalAcademyofSciences,aFellowof
theAmericanAcademyofArtsandSciences,amemberoftheNeurosciencesResearchProgram,aFellow
oftheAmericanAcademyofNeurology,amemberoftheEuropeanAcademyofSciencesandArtsandof
theRoyal AcademyofMedicineinBelgium,amember oftheAmerican Neurological Associationandof
the Association of American Physicians, and a board member of leading neuroscience journals. He has
receivednumerousscientificprizesanddeliveredsomeofthemostprestigiouslecturesintheUnitedStates
andinEurope.HisbookDescartes’Error:Emotion,ReasonandtheHumanBrain(Putnam,1994)istaught
inuniversitiesworldwide.HisnewbookTheFeelingofWhatHappens:Body,Emotion,andtheMakingof
Consciousness, published by Harcourt, has received several awards and has been translated into 18
languages.
Martha J. Farah
University of Pennsylvania
MarthaJ.FarahistheBobandArleneKogodProfessorofPsychologyandtheDirectoroftheCenterfor
CognitiveNeuroscienceattheUniversityofPennsylvania.Sheisknownforherworkontheneuralbases
of human perception and cognition, described in over a hundred research publications as well as in five
books.Hercurrentinterestsareinemotion–cognitioninteractionanddevelopment.Dr.Farah’sworkhas
been honored witha number ofawards,including theAmerican PsychologicalAssociation Distinguished
Scientific Award for an Early Career Contribution, the National Academy of Sciences Troland Research
Award, and a Guggenheim Fellowship.
Michael F. Huerta
National Institute of Mental Health
Michael F. Huerta received both his B.A. in zoology and his Ph.D. in anatomy from the University of
WisconsininMadison.HewasapostdoctoralfellowatVanderbiltUniversity,servedonthefacultyofthe
University of Connecticut Health Center, and was a guest researcher in the intramural program of the
National Institute of Mental Health at the National Institutes of Health. Most of Dr. Huerta’s research
publications concern sensorimotor integration at the systems level of analysis. He is currently Associate
Director of the Division of Neuroscience and Basic Behavioral Research and Director of the Office of
Translational Research and Scientific Technology at the National Institute of Mental Health.
Dr. Huerta’s research efforts are focused on integrating the many disciplines, perspectives, and
approaches that comprise neuroscience. He also has significant interest in advancing the research and
development of technologies useful to brain researchers, particularly informatics tools. Dr. Huerta has
received numerous awards for his leadership in areas including neuroscience, imaging, informatics, and
bioengineering. He continues to review manuscripts for journals, edits scientific books, and serves as an
editor on the new journal Neuroinformatics.
Sue Iversen
University of Oxford
Sue Iversen is professor of experimental psychology and Pro-Vice-Chancellor for Planning and Resource
AllocationattheUniversityofOxford.ShestudiedforherundergraduatedegreeandPh.D.atCambridge,
thenspentherpostdoctoralyearsintheUnitedStatesattheNationalInstitutesofHealthandatHarvard
Medical School. She was formerly Research Director at the U.S. pharmaceutical company Merck & Co.,
whereshewasinvolvedinestablishingthelargestcommercialNeuroscienceResearchCentreintheUnited
Kingdom, based at Harlow in Essex, and has previously held research posts at Cambridge University.
Dr.Iversen’sresearchandpublicationsfocusondisordersofbrain function,particularlyschizophrenia
and Alzheimer’s disease with particular reference to the biological bases of these disorders, their clinical
presentation,andtreatment.Shehaspublished307papers,edited24volumes,andisco-authorwithL.L.
IversenofBehaviouralPharmacology.UntilrecentlyshewasEditor-in-ChiefofNeuropsychologiaandhas
held senior office in a number of professional psychological and neuroscience societies.
Edward G. Jones
University of California, Davis
EdwardG.JonesreceivedhisMedicalDegreefromtheUniversityofOtago,NewZealand,andhisPh.D.
fromOxfordUniversity.Heisanauthorityonbrainanatomyandisrecognizedasaleadingresearcherof
the central nervous system. He was a leading figure in introducing molecular biology methodology to
systems neuroscience, and has done groundbreaking work on schizophrenia, focusing on how changes at
the molecular and cellular level are associated with the disorder. Dr. Jones also belongs to a group of
scientists who are working on the U.S. Human Brain Project, which supports the development of
databases on the brain and development of technologies to manage and share neuroscience information.
HewasafoundingmemberoftheFrontierResearchPrograminBrainMechanismsofMindandBehavior
at Riken, Japan.
Dr.Jones’manyawardsincludetheCajalmedalforexcellenceinresearchandKriegCorticalDiscoverer
(1989),theHenryGrayAward,AmericanAssociationofAnatomists(2001),andtheKarlSpencerLashley
Award, American Philosophical Society (2001). He has served as the President of the Society for
Neuroscience,isaFellowoftheAmericanAssociationfortheAdvancementofScience,andisanoriginal
memberoftheThomsonScientificISIHighly-CitedResearchers.HeiscurrentlytheDirectoroftheCenter
for Neuroscience at the University of California, Davis.
Jon H. Kaas
Vanderbilt University
Jon H.Kaas isaDistinguished, Centennial ProfessorofPsychologyatVanderbiltUniversity, whereheis
alsoprofessorofcellbiology.HeisanelectedmemberoftheNationalAcademyofSciences,theAmerican
Academy of Arts and Sciences, and the Society of Experimental Psychologists. He has received the
Sutherland Prize for Achievement in Research, the Javits Neuroscience Investigator Award, the Krieg
Cortical Discoverer Award, and the American Psychological Association Distinguished Scientific
Contribution Award.
OneofDr.Kaas’majorresearchinterestsishowsensory-perceptualandmotorsystemsareorganizedin
mammalian brains, especially those of primates. This interest has led to comparative studies of primate
brains and efforts to infer the course of human brain evolution. Related research efforts have revealed
aspects of brain specializations in mammals with unusual adaptations such as moles and bats. Another
researchfocushasbeentheplasticityofdevelopingandmaturesensoryandmotorsystemswitheffortsto
determine mechanisms of brain reorganization and recovery after sensory loss.
Raja Parasuraman
The Catholic University of America
Raja Parasuraman is Director of the Cognitive Science Laboratory, and professor of psychology at The
Catholic University of America in Washington, D.C. He received a B.Sc. (1st Class Honors) in electrical
engineeringfromImperialCollege,UniversityofLondon,UK(1972)andanM.Sc.inappliedpsychology
(1973) and a Ph.D. in psychology (1976) from the University of Aston, Birmingham, UK. Dr.
Parasuraman has carried out research on attention, automation, aging and Alzheimer’s disease, event-
related brain potentials, functional brain imaging, signal detection, vigilance, and workload. His books
includeThePsychologyofVigilance(AcademicPress,1982),VarietiesofAttention(AcademicPress,1984),
Event-Related Brain Potentials (Oxford University Press, 1990), Automation and Human Performance
(Erlbaum, 1996), and The Attentive Brain (MIT Press, 1998).
Dr. Parasuraman served as a member of the Human Development and Aging Study Section of the
National Institutes of Health from 1992 to 1995, and was a member of the National Research Council’s
Panelon Human Factors inAir-Traffic ControlAutomation from 1994to 1998. He iscurrentlyChairof
the National Research Council Panel on Human Factors. He is also on the editorial board of several
journals, including Neuropsychology and Human Factors. Dr. Parasuraman was elected a Fellow of the
American Association for the Advancement of Science (1994), the American Psychological Association
(1991), the American Psychological Society (1991), and the Human Factors and Ergonomics Society
(1994).
Michael I. Posner
University of Oregon
MichaelI.PosnerisProfessorEmeritusattheUniversityofOregonandiscurrentlyDirectoroftheSackler
InstituteforDevelopmentPsychobiologyattheWeillMedicalCollegeofCornellUniversityinNewYork.
Since the mid-1960s, Dr. Posner has been involved in the effort to measure human thought and to
understanditsphysicalbasis.His1978bookChronometricExplorationsofMindwasselectedasoneofthe
most influential books in cognitive science. Dr. Posner joined with Marcus Raichle at Washington
Universityinneuroimagingstudiesthatservedtolocalizebrainnetworksofcognitiveprocessesinnormal
subjects. Their book in this field, Images of Mind, received the 1996 Williams James award for the most
outstanding volume in the field of psychology. They jointly received awards from the Dana Foundation
andtheAmericanPhilosophicalSociety,andreceivedthePasarowandGrawenmeyerawardsforresearch
contributionstounderstandingmentalprocesses.CurrentlyDr.Posnerisworkingwithmanycolleaguesat
theSacklerInstituteandtheUniversityofOregontoexaminetheanatomyandcircuitryofattention and
self regulation in infants and children.
Henry C. Powell
University of California, San Diego
HenryC.PowellisagraduateofUniversityCollegeDublinandtheNationalUniversityofIreland(M.B.,
B.Ch., B.A.O., 1970). He was awarded the degrees of M.D. (1985) and D.Sc. (1994) based on published
workinpathology.Dr.PowellisalsoaFellowoftheRoyalCollegeofPathologists(UK).Heinternedin
pathologyandmedicineatPhiladelphiaGeneralHospital(1970–1971)andcompletedresidencytrainingin
AnatomicandClinicalPathologyattheUniversityofCalifornia,SanDiegofrom1971to1975.Hehelda
fellowship in neuropathology at Massachusetts General Hospital (1975–1976), prior to being appointed
assistant professorof pathologyatthe UniversityofCalifornia, San Diego. Currentlyhe isprofessor and
interimchairmanofthedepartmentofpathologyandheadofthedivisionofneuropathologyandelectron
microscopy.
Dr.Powell’sresearchinterestsarefocusedonmetabolic,inflammatory,anddegenerativediseasesofthe
nervous system, with emphasis on the pathogenesis of peripheral neuropathies in diabetes. He and his
collaborators study experimentally induced neuropathy in diabetic rats as well as the nervous system
effects of spontaneously occurring diabetes in feline and human disease.
John Smythies
University of California, San Diego
John Smythies is a graduate of the University of British Columbia, where he was awarded an M.Sc. in
neuroanatomy, philosophy, and anthropology, and of Cambridge University, where he was awarded the
degrees of M.Sc. in psychology and M.D. He is currently Director of the Division of Neurochemistry at
the Center for Brain and Cognition as well as a research scientist in the department of psychology at the
University of California, San Diego. He is also a senior research fellow at the Institute of Neurology at
National Hospital in London and a visiting professor in the department of psychiatry at Harvard
University.
Dr. Smythies is a member of numerous scientific societies and editorial boards in neuroscience and
neuropsychiatry. He has authored 244 publications in neuroscience and medicine and has written 12
books. His main research interests are the neurochemistry of schizophrenia, redox mechanisms in the
brain, the biochemical basis of synaptic plasticity, and the mind-brain problem.
Elizabeth Warrington
The National Hospital for Neurology and Neuroscience
ElizabethWarringtonhasbeenassociatedwithLondonUniversitysince1951.ShewasawardedaB.Sc.in
1954, a Ph.D. in 1960 and a D.Sc. in 1975. She joined the staff of the Institute of Neurology in 1954 in a
research capacity. In 1972 Dr. Warrington was appointed head of the department of clinical
neuropsychology, a post she held until she retired in 1996. In addition to her clinical duties she has
pursued an active research career with special interests in perception, memory, and language disorders.
Dr. Warrington was elected to the Fellowship of the Royal Society in 1986, and she has been awarded
honorary degrees from the Universities of Bologna, Italy, and York, UK. At present she is an honorary
consultant neuropsychologist to the Dementia Research Group where she is engaged in active research.
Jeremy M. Wolfe
Brigham & Women’s Hospital
Jeremy M. Wolfe became interested in vision research during the course of a summer job at Bell Labs in
New Jersey after his senior year in high school. He graduated summa cum laude from Princeton in 1977
with a degree in psychology and went on to obtain his Ph.D. in 1981 from MIT, studying with Richard
Held. His Ph.D. thesis was entitled ‘‘On Binocular Single Vision.’’ Dr. Wolfe remained at MIT as a
lecturer,assistantprofessor,andassociateprofessoruntil1991.Duringthatperiod,hepublishedpaperson
binocularrivalry,visualaftereffects,andaccommodation.Inthelate1980s,thefocusofthelabshiftedto
visual attention—a transition marked most clearly by the publication of the first version of Dr. Wolfe’s
‘‘Guided Search’’ model of visual search in 1989. Since that time, he has published numerous articles on
visual search and visual attention.
In 1991, Dr. Wolfe moved to Brigham and Women’s Hospital and Harvard Medical School, where he
remainstothepresentday.HecontinuestoteachintheMITConcourseProgram.Dr.Wolfehasservedin
editorial capacities for a number of journals, currently as Associate Editor of Perception and
Psychophysics. He is member of the National Institutes of Health VIS-B Study Section, and is President
oftheEasternPsychologicalAssociation.Dr.WolfewontheBakerMemorialPrizeforteachingatMITin
1989. He is a Fellow of the American Psychological Association and a member of the Society for
Experimental Psychologists.
Editor-in-Chief
V. S. Ramachandran
University of California, San Diego
V.S.RamachandranisDirectoroftheCenterforBrainandCognitionandprofessorofneuroscienceand
psychologyatthe Universityof California, San Diego.He isadditionally anadjunct professorof biology
attheSalkInstitute.HeobtainedanM.D.fromStanleyMedicalCollegeandaPh.D.fromTrinityCollege
at the University of Cambridge, where he was elected a senior Rouse Ball Scholar.
He has received many honors and awards, including a fellowship from All Souls College, Oxford, an
honorary doctorate from Connecticut College, a Gold Medal from the Australian National University,
and the Ariens Kappers Medal from the Royal Nederlands Academy of Sciences for landmark
contributions in neuroscience.
Dr. Ramachandran’s early research was on visual perception, but he is best known for his work in
neurology.In1995hegavetheDecadeoftheBrainLectureatthe25thannual(SilverJubilee)meetingof
the Society for Neuroscience. More recently he gave the inaugural keynote lecture at the Decade of the
BrainConferenceheldbytheNationalInstituteofMentalHealthattheLibraryofCongress.Healsogave
the first Hans Lucas Teuber lecture at MIT, the Rudel-Moses lecture at Columbia, the Dorcas Cumming
(inauguralkeynote)lectureatColdSpringHarbor,theRaymondAdamslectureatMassachusettsGeneral
Hospital,Harvard,andthepresidentialkeynotelectureattheannualmeetingoftheAmericanAcademyof
Neurology.
Dr. Ramachandran has published over 120 papers in scientific journals, including three invited review
articlesinScientificAmerican,andiseditor-in-chiefofAcademicPress’acclaimedEncyclopediaofHuman
Behavior. His work is featured frequently in the major news media, and Newsweek magazine recently
named him a member of ‘‘the century club’’: one of the hundred most prominent people to watch in this
century.
Action Potential
JOHNA.WHITE
BostonUniversity
I. BasicPropertiesoftheActionPotential voltage clamp An experimental protocol in which membrane
potentialiscontrolled,usuallyinastepwisefashion,andresulting
II. ClassicalDescriptionsoftheActionPotential
transmembranecurrentsaremeasured.
III. CurrentTopicsRelatedtotheActionPotential
voltage-gatedionchannels Transmembraneproteinsthatopen
inresponsetochangesinmembranepotential,allowingaparticular
ionicspeciestocrossthemembrane.
GLOSSARY
The action potential is the all-or-nothing electrical impulse
activation The time-dependent growth of a membrane conduc-
used to communicate information between neurons
tanceinresponsetomembranedepolarization.
andfromneuronstomusclefibers.Theenergyusedto
all-or-nothing A term that refers to the property that action
generate action potentials is in the form of electro-
potentials, if they occur, have a stereotyped shape that is largely
chemical gradients of ions (in particular, sodium and
independentofthesizeandformofthesuprathresholdstimulus.
potassium) that are established by ion pumps. The
currentclamp Anexperimentalprotocolinwhichtransmembrane
rising phase of action potentials is caused by the
current is controlled, usually at a series of constant values, and
resultingtransmembranepotentialsaremeasured. autocatalytic activation of many Na+-selective ion
deactivation Thetime-dependentreversalofactivationinresponse channels in response to sufficiently large increases in
tomembranehyperpolarization;leadstoadecreaseinmembrane membrane potential. The falling phase of the action
conductance. potential is caused by two factors that develop more
deinactivation Thetime-dependentreversalofinactivation,trig- slowlybutdominatetheelectricalresponseafterafew
gered by hyperpolarization; leads to an increase in membrane milliseconds:theinactivationofsodiumchannelsand
conductance. the activation of potassium channels, both of which
depolarization Makingmembranepotentiallessnegative. occur in response to depolarization. Understanding
hyperpolarization Makingmembranepotentialmorenegative. thediversemechanismsunderlyingelectricalexcitabil-
inactivation Thetime-dependentdeclineofaconductance(e.g.,the ityinneuronsremainsarichfieldofexperimentaland
Na+conductance),whichfollowsafteritsactivation;triggeredby theoretical study, with wide-ranging implications for
depolarization. humanhealth.
membrane potential The voltage difference across the neural
membrane, determined by the balance of ionic fluxes across the
plasmamembrane. I. BASIC PROPERTIES OF THE
refractoryperiod Theperiodimmediatelyafteranactionpoten- ACTION POTENTIAL
tial,inwhichitisdifficultorimpossibletoinduceasecondaction
potential.
spaceclamp Theconditioninwhichmembranepotentialisthe The basic properties of the action potential can be
samethroughoutthespatialextentofthecell. studied using a microelectrode constructed from a
threshold Thevalueofmembranecurrentormembranepotential glass capillary tube with a fine tip and containing
necessarytoinduceanactionpotential. artificial intracellular solution. This microelectrode,
EncyclopediaoftheHumanBrain Copyright2002,ElsevierScience(USA).
1
Volume1 Allrightsreserved.
2
ACTIONPOTENTIAL
insertedintothecellbodyoraxonofaneuron(Fig.1a, potentialquicklyrisestoavaluewellabove0mVand
inset), measures the value of membrane potential then falls over the course of 1–5msec to its resting
relative to the extracellular space. At rest, typical value(Fig.1a,middle).Often,thefallingphaseofthe
values of membrane potential range from (cid:1)40 to action potential undershoots resting potential tem-
(cid:1)90mV.Passingpositiveelectricalcurrentintothecell porarily. The action potential is said to be all-or-
depolarizes it (i.e., makes membrane potential less nothing because it occurs only for sufficiently large
negative). In response to small depolarizing stimuli, depolarizing stimuli, and because its form is largely
theneuron’sresponseissmallaswell(Fig.1a,bottom). independentofthestimulusforsuprathresholdstimu-
Inresponsetolargerstimuli,aboveathresholdvalue, li. In some neurons, a single action potential can be
theresponseisfundamentallydifferent;themembrane induced by the offset of a hyperpolarizing stimulus
a c
30
25
Applied Current 2m )
I0 c 20
A/
d ( 15
ol
h
es 10
I = 20 A/cm2 25 mV hr
0 T
5
2.5 ms
0
I = 5 A/cm2 0 2 4 6 8 10
0
Stimulus Duration (ms)
d
250
ARP
b RRP
200
Applied Current I0 2cm ) 150
A/
d ( 100
ol
h ISI
s
e
25 mV hr 50
T
2.5 ms
I = -10 A/cm2 0
0
0 5 10 15 20 25
Interstimulus Interval (ms)
Figure 1 Basic properties of the action potential. (a) Traces show responses of a simulated space-clamped squid axon (T¼6.31C) to
intracellularlyinjectedcurrentpulsesofduration0.5msec(toptrace).Thesimulatedrecordingconfigurationisshownintheinset.Sufficiently
largeinputsevokeall-or-nothingactionpotentials(middletrace).Theresponseisminimaltosubthresholdstimuli(bottomtrace).Theinset
showsthebasicrecordingconfiguration.(b)Asimulationdemonstratinganode-breakexcitationinresponsetotheoffsetofahyperpolarizing
currentpulse(duration¼10msec).(c)Currentthreshold(theminimalamplitudeofacurrentstepnecessarytoevokeanactionpotential)
plottedvsstimulusduration.(d)Simulationresultsdemonstratingrefractoriness.Twocurrentpulses(duration¼0.5mseceach)weredelivered
tothemodel,withinterstimulusinterval(ISI)variedsystematically.Thefirstpulsehadmagnitudetwicethethresholdforevokinganaction
potential.They-axisshowsthemagnitudeofthesecondpulsenecessarytoevokeaspike.ForISIo15msec,thresholdisaboveitsnormalvalue
(dashedline).Duringtherelativerefractoryperiod(RRP),thresholdiselevated;duringtheabsoluterefractoryperiod(ARP),itisnotpossible
toevokeasecondactionpotential.
3
ACTIONPOTENTIAL
a b
140
120
20 A/cm2
s ) 100
s/
e
k 80
pi
s
e ( 60
at
7 A/cm2 20 mV g R 40
5 ms Firin 20
0
0 A/cm2 -20
-10 0 10 20 30 40 50 60 70 80
I ( AA//ccmm22 )
app
Figure2 Spikeratedependsonthemagnitudeofappliedcurrent.(a)Simulatedtracesofspace-clampedsquidgiantaxon(T¼6.31C)to
constantappliedcurrent.(b)Firingrateincreaseswithincreasingappliedcurrent.Notethattheminimalfiringrateiswellabovezerospikes/sec.
(Fig. 1b). This phenomenon is called anodal break onenodeofRanviertothenext,greatlyincreasingthe
excitationorreboundspiking. speedofpropagation.
The value of threshold depends on the duration of
thestimulus(Fig.1c);briefstimuli arerequiredtobe
larger to evoke an action potential. Threshold also II. CLASSICAL DESCRIPTIONS OF THE
dependsonmoresubtlefeaturesofthestimulus,such ACTION POTENTIAL
asitsspeedofonset.Forashorttimeafteranaction
potential has occurred, it is impossible to evoke a
A. Electrochemical Potentials and Voltage-
secondone(Fig.1d).Thisperiodisreferredtoasthe
Dependent Membrane Conductances
absolute refractory period (ARP). After the ARP
comes the relative refractory period (RRP), in which
anactionpotentialcanbeevoked,butonlybyalarger Changes in electrical potential in excitable cells are
stimulus than was required to evoke the first action driven by movement of ions through ion-specific
potential. Stimulation by an ongoing suprathreshold membrane conductances. For a perfectly specific
stimulus leads to repetitive firing at a rate that is conductance G, the current across the membrane
constantonceanytransientshavesettledout(Fig.2a). I¼G (cid:2) (Vm(cid:1)Vn),whereVmistheelectricalpotential
The rate of repetitive firing increases with increasing across the membrane and Vn is the equilibrium
depolarization (Fig. 2b), eventually approaching the potentialfortheion,givenbytheNernstequation:
(cid:1) (cid:2)
limitimposedbytheARP. RT ½X (cid:3)o
Once initiated, the action potential propagates Vn ¼z Fln ½Xn(cid:3)i
n n
downtheaxonatanapproximatelyconstantvelocity.
The leading edge of the action potential depolarizes where R¼8.314 J/(molK) is the gas constant, T is
adjacent unexcited portions of the axon, eventually absolute temperature, zn is the valence of ion n,
bringingthemtothreshold.Inthewakeoftheaction F¼9.648 (cid:2) 104C/mol and is Faraday’s constant,
potential, the membrane is refractory, preventing [Xn]o is the outer concentration of ion n, and [Xn]i is
reexcitation of previously active portions of the cell. the inner concentration of ion n. Intuitively, the
In unmyelinated axons, the action potential travels equilibrium potential is the value of membrane
smoothly, with constant shape and at constant velo- potential at which ionic fluxes due to concentration
city.Inmyelinatedaxons,conductionissaltatory:The gradients and voltage gradients cancel one another,
actionpotential‘‘jumps’’nearlyinstantaneouslyfrom leading to zero net flux of the ion. Note that ionic