Memories: Molecules and Circuits

188 Pages·2007·8.461 MB·English

by  Peter J. Bayley, Larry R. Squire (auth.), Bruno Bontempi Ph.D., Alcino J. Silva, Yves Christen Ph.D. (eds.)

researchandperspectivesinneurosciences
FondationIpsen
Editor
YvesChristen,FondationIpsen,Paris(France)
EditorialBoard
AlbertAguayo,McGillUniversity,Montreal(Canada)
PhilippeAscher,EcoleNormaleSupérieure,Paris(France)
AlainBerthoz,CollègedeFrance,CNRSUPR2,Paris(France)
Jean-MarieBesson,INSERMU161,Paris(France)
EmiliaBizzi,MassachusettsInstituteofTechnology,Boston(USA)
AndersBjorklund,UniversityofLund(Sweden)
FloydBloom,ScrippsClinicandResearchFoundation,LaJolla(USA)
JoëlBockaert,CentreCNRS-INSERMdePharmacologieEndocrinologie,
Montpellier(France)
PierreBuser,InstitutdesNeurosciences,Paris(France)
Jean-PierreChangeux,CollègedeFrance,InstitutPasteur,Paris(France)
CarlCotman,UniversityofCalifornia,Irvine(USA)
StevenDunnett,UniversityofCambridge,Cambridge(UK)
GeorgeFink,MedicalResearchCouncil,Edingburgh(UK)
FredGage,SalkInstitute,LaJolla(USA)
JacquesGlowinski,CollègedeFrance,Paris(France)
ClaudeKordon,INSERMU159,Paris(France)
MichelLacour,CNRSURA372,Marseille(France)
MichelLeMoal,INSERMU259,Bordeaux(France)
GaryLynch,UniversityofCalifornia,Irvine(USA)
BrendaMilner,McGillUniversity,Montreal(Canada)
JohnOlney,WashingtonUniversityMedicalSchool,SaintLouis(USA)
AlainPrivat,INSERMU336,Montpellier(France)
AlienRoses,DukeUniversityMedicalCenter,Durham(USA)
ConstantinoSotelo,INSERMU106,Paris(France)
Jean-DidierVincent,InstitutAlfredFessard,CNRS,Gif-sur-Yvette(France)
BrunoWill,CentredeNeurochimieduCNRS/INSERMU44,
Strasbourg(France)
B. Bontempi A. Silva
Y. Christen (Eds.)
Memories:
Molecules and
Circuits
With61Figures
123
Bontempi,Bruno,Ph.D.
LaboratoiredeNeurosciencesCognitives
CNRSUMR5106
UniversitédeBordeaux1
AvenuedesFacultés
33405Talence
France
e-mail:[email protected]
Silva,AlcinoJ.,Prof.Dr. Christen,Yves,Ph.D.
DepartmentsofNeurobiology FondationIPSEN
PsychiatryandBiobehavioralSciences PourlaRechercheThérapeutique
PsychologyandBrainResearchInstitute 24,rueErlanger
695YoungDriveSouth 75781ParisCedex16
Room2357Box951761,UCLA France
LosAngeles,CA90095-1761 e-mail:[email protected]
USA
e-mail:[email protected]
ISBN 978-3-540-45698-8 SpringerBerlinHeidelbergNewYork
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Preface
Memorycanbetypicallydefinedasthebrainfunctionenablingtheencoding,storage
and retrieval of sensory information. In operational terms, this definition implies
thatourcentralnervoussystemnotonlyprocessesvarioussensorymodalities,bethey
visual,tactile,auditory,olfactoryorgustatory,butisalsocapableofforming,organizing
and conservingmemory traces for extended periods of time. At both psychological
andphysiologicallevels,thereisnowaconsensusthatmemorymustnolongerbeseen
asaunitaryphenomenonbutratherasanensembleofdynamicprocesses,eachone
beingsubservedbydifferentbrainregionsorganizedintomultiplememorysystems
thatsupportdifferentformsofmemoryandthatconstantlyinteracttoensureoptimal
performanceduringanygivencognitivechallenge.
Despiteremarkableprogressachievedoverthelast30yearsinourunderstanding
oftheneuralbasesofcognitiveprocessesandassociatedpathologies,thequestionsof
how,whereandwhenmemorytracesareformedinthebrainremaincentralissuesand
continuetofuelmuchdebateinthefieldofcognitiveneuroscience.Howdoneuronal
systemsencode,consolidateandretrievememory?Howarememoriesembeddedinto
complexneuronalnetworks?Howdomolecularmechanismsmodulatetheneuronal
plasticityandfunctioningofthesenetworksduringmemoryprocessing?Whatarethe
fundamentalunitsofcomputationinthebrain?Thankstothedevelopmentofnovel
approaches,includingtransgenictechniques,functionalbrainimaging,multiplecell
recording,functionalgenomicsandproteomics,thelastdecadehaswitnesseddramatic
advancesintheneurobiology,neuroanatomy,neurophysiologyandneuropathologyof
learningandmemoryprocesses.ThemainaimoftheColloqueMédecineetRecherche,
titled“Memories:MoleculesandCircuits,”organizedbytheFondationIpseninParis
onApril24,2006,anduponwhichthepresentsetofchaptersisbased,wastosurvey
these recent advances and to provide an integrative view of molecular, cellular, and
systemslevelmechanismsunderlyingcognitiveprocessesinanimals,nonhumanpri-
matesandhumans.Duringtheconference,currentstateoftheartandfutureavenues
werediscussedbydistinguishedspeakerswhoprovidednotonlyanoverviewofthe
underlyingneurobiologyofcognitiveprocessesfromabasicsciencestandpointbut
alsofocusedonclinicalandtherapeuticaspectssurroundingimpairmentsassociated
withdisordersthataffectcognition.Viewsfromthesedifferentspeakersarereflected
here in the form of eleven chapters that tackle key issues in the field of cognitive
neuroscience.
Studiesofbrain-damagedpatientshaveprovidedremarkableinsightsintotheneu-
roanatomyofmemoryandintohowmemoriesareorganizedandstoredinthebrain.
Onechapterillustratesthislineofstudiesandfocusesontheroleofthemedialtempo-
rallobe,includingthehippocampus,withrespecttodifferentmemoryformssuchas
VI
declarativememory(i.e.,consciousmemoryforfactsandevents)andnondeclarative
memory (i.e., unconscious memory for skills and habits that is independent of the
medialtemporallobe).Interestingly,thedatareviewedpointtoatime-limitedrolefor
thehippocampalregioninremotememorystorage.Whilethemedialtemporallobeis
crucialforacquiringnewmemories,itdoesnotappeartoberequiredtorecollectde-
tailedautobiographicalmemoriesacquiredlongago,thisfunctionbeingprogressively
subsumed by extrahippocampal structures, namely widespread cortical regions, as
memoriesmatureovertime.Convergingevidencehasalsobeenfoundinexperimental
animals,asdetailedinanotherchapterthatfocusesonthedynamicsofhippocampal-
corticalinteractionsduringthecourseofthememoryconsolidationprocessthatare
requiredfortheformationofenduringmemories.Functionalbrainimagingstudies
alongsidepharmacologicalapproachesandtraditionallesiontechniqueshaveprovided
newbreakthroughsintheidentificationofthebrainregionsunderlyingtheorganiza-
tionofrecentandremotememories.Whiletheneuronalmechanismsdrivingmemory
consolidationcontinuetobehotlydebated,itisnowacknowledgedthattheformation
oflong-lastingmemoriesisnolongertobeseenasasimplepassivephenomenonbut
ratherasadynamicprocessofcontinuousneuronalreorganizationasnewmemories
arebeingprocessedandsubsequentlystored.
Howcanweunravelthecellularandmolecularmechanismsunderlyingthefor-
mation of enduring memories? Performing genetic manipulations to control gene
expressioniscertainlyonepowerfulapproachtodissecttheplethoraofsignalingpath-
waysthatleadtomemoryformation.Onechapterillustratesthistypeofapproachand
providesconvincingevidencethatDrosophilaconstitutesavalidandintegrativeinsect
modeltostudysomeofthecellularmechanismsinvolvedinnormalorpathological
humanmemory.Ashighlightedinanotherchaptercenteredonthemolecularbasesof
remotememoryinthemouse,experimentalstudieshavestartedtosuccessfullyidentify
specificmechanismsandunderlyingmoleculesthatgovernstructuralsynapticplastic-
ityatboththehippocampalandcorticallevels,asmemoriesprogressivelygainstability.
Whathappenswhenremotelyacquiredmemoriesarereactivated?Memoriesmay
never be stored in a definitive form but continuously reorganized and restabilized
each time they are retrieved. In this respect, the very term “consolidation” may be
misleading.Indeed,uponreactivation,corticalmemorieshavebeenshowntobecome
labileagainandtorequireanotherroundofproteinsynthesistoregainstability.Two
chapterstacklethiscriticalissueandprovideexcitingevidencethatdisruptionofthe
so-called process of “memory reconsolidation” may be a valid therapeutic strategy
for treating maladaptive memory disorders such as post-traumatic stress and drug
addiction.
How are memories encoded and stored? Such processes necessarily involve the
constitutiveunitsofthebrain,namelyneurons,whichareorganizedintocomplex,in-
terconnectedcellassemblies.Plasticityphenomenaintheformofchangesinsynaptic
efficacywithinexistingsynapsesorsynthesisofnovelsynapsescanreadilyoccurwithin
thesecellassemblies.Significantadvanceshavebeenachievedinthesearchoftheneu-
ronal code of memories using large-scale electrophysiologicaltechniques that allow
fortherecordingofmultipleneuronalensembles(upto260neurons)simultaneously
inthefreelymovingrodentornonhumanprimateconfrontedwithvariouscognitive
challenges.Threechaptersinthisbookproviderepresentativeexamplesofthiskindof
approachwhich,fromaconceptualpointofview,highlightthehighselectivity,hierar-
VII
chyandcooperationbetweenhippocampalandcorticalneuronsinidentifyingspecific
stimuli,analyzingtheoutcome(successorfailure)ofthebehavioralresponse,andcon-
verting daily experiences into various memory forms. Highly integrative properties
of hippocampal-corticalcellassembliesthatcanact asbasiccodingunitsprovidea
networkmechanismforthebraintoachievelargememorystoragecapacityandhigher
cognitivefunctions,suchasassociation,abstractionorgeneralization,aswellasthe
representationofspaceintermsofposition,directionandvelocity.
Howisourbraincapableofcoordinatingthoughtsandactioninrelationtointernal
goals?Asreviewedinanotherchapter,onespecificregioninthebrain,theprefrontal
cortex,seemstoplayaprivilegedroleinexertingthistypeofcognitivecontrol.This
regionappearstosubservehigher-orderknowledgeandisparticularlywellsuitedfor
acquiringabstractrulesandconceptsneededtoguidecomplex,goal-directedbehaviors
ofthekindobservedinnonhumanprimatesandhumans.
The growing knowledge of the cellular and molecular mechanisms underlying
memory function also has opened the door to new therapeutic strategies for the
treatmentofneuropsychiatricdisorders.Onelastchapternicelyillustratessuchnovel
strategiesbypointingtonewmoleculesthatdisruptmemorycircuitsinAlzheimer’s
diseaseandbyidentifyingnoveltargetsforalleviatingthecognitivedeficitsassociated
withthisneurodegenerativedisease.
Overall,wehopethatthedifferentchaptersinthisbookwillofferacomprehensive
andup-to-dateoverviewofthecurrentknowledgeabouttheneuroanatomyofmem-
oryanditsunderlyingcellularandmolecularmechanisms.Clearly,mechanismsthat
governmemory processesareincrediblycomplexandavastarrayofquestionsstill
remainstobeaddressed.However,thesetofchapterspresentedherealsodemonstrate
thatthefieldofmemoryresearchismovingforwardatarapidpace.Byincreasingly
relyingonintegrativeapproachesthatinvolvecross-speciesanalysesandacombina-
tion of multiple levels of analyses, ranging from innovative cognitive paradigms to
state-of-the-artcellularandmoleculartechniques,thereisnodoubtthatongoingand
futurestudieswillcontinuetobesuccessfulinsheddingnewlightonthisfascinating
fieldofresearch.
Finally,wewouldliketotakethisopportunitytothankJacquelineMervaillie,San-
draMarchandandtheothercontributingmembersoftheFondationIpsenfortheir
outstandingskillsintheorganizationofthisColloqueMédecineetRecherche.Weare
alsogratefultoMaryLynnGageforherexcellenteditorialassistanceduringtheprepa-
rationofthisbook.
BrunoBONTEMPI
AlcinoJ.SILVA
YvesCHRISTEN
TableofContents
TheNeuroanatomyandNeuropsychologyofDeclarative
andNondeclarativeMemory
P.J.Bayley,L.R.Squire .................................................... 1
DynamicsofHippocampal-CorticalInteractions
DuringMemoryConsolidation:InsightsfromFunctionalBrainImaging
B.Bontempi,T.P.Durkin.................................................. 19
FromMoleculetoMemorySystem:
GeneticAnalysesinDrosophila
G.Isabel,D.Comas,T.Preat............................................... 41
TowardsaMolecularandCellularUnderstandingofRemoteMemory
B.J.Wiltgen,R.A.M.Brown,L.E.Talton,A.J.Silva ............................ 59
Post-ActivationState:ACriticalRiteofPassageofMemories
Y.Dudai ............................................................... 69
Reactivation-DependentAmnesia:DisruptingMemoryReconsolidation
asaNovelApproachfortheTreatmentofMaladaptiveMemoryDisorders
J.L.C.Lee,B.J.Everitt ..................................................... 83
TheOrganizingPrinciplesofReal-TimeMemoryEncoding:
NeuralCliqueAssembliesandUniversalNeuralCodes
J.Z.Tsien ............................................................... 99
MakingandRetainingNewMemories:TheRoleoftheHippocampus
inAssociativeLearningandMemory
W.A.Suzuki ............................................................ 113
EntorhinalGridCellsandtheRepresentationofSpace
F.Sargolini,E.I.Moser ................................................... 125
ThePrefrontalCortex:Categories,Concepts,andCognitiveControl
E.K.Miller .............................................................. 137
MoleculesthatDisruptMemoryCircuitsinAlzheimer’sDisease:
β
TheAttackonSynapsesbyA Oligomers(ADDLs)
W.L.Klein,P.N.Lacor,F.G.DeFelice,S.T.Ferreira ............................ 155
SubjectIndex ........................................................... 181
Contributors
Bayley,PeterJ.
VAMedicalCenter(116A),3350LaJollaVillageDrive,SanDiego,CA92161,USA
Bontempi,Bruno
LaboratoiredeNeurosciencesCognitives,CNRSUMR5106,UniversitédeBordeaux1,
AvenuedesFacultés,33405Talence,France
Brown,RobertA.M.
DepartmentsofNeurobiology,PsychiatryandBiobehavioralSciences,Psychologyand
BrainResearchInstitute,695YoungDriveSouth,Room2357Box951761,UCLALos
Angeles,CA90095-1761,USA
Comas,Daniel
GènesetDynamiquedesSystèmesdeMémoire,CNRSUMR7637,ÉcoleSupérieurede
PhysiqueetChimieIndustrielle,10RueVauquelin,75005Paris,France
DeFelice,FernandaG.
CognitiveNeurology&Alzheimer’sDiseaseCenter,NorthwesternUniversityInstitute
forNeuroscience,633ClarkStreet,Evanston,IL60208,USA
Dudai,Yadin
DepartmentofNeurobiology,TheWeizmannInstituteofScience,Rehovot76100,Israel
Durkin,ThomasP.
LaboratoiredeNeurosciencesCognitives,CNRSUMR5106,UniversitédeBordeaux1,
AvenuedesFacultés,33405Talence,France
Everitt,BarryJ.
DepartmentofExperimentalPsychology,MRC/WellcomeTrustBehaviouralandClin-
icalNeuroscienceInstitute,UniversityofCambridge,DowningStreet,CambridgeCB2
3EB,UK.
Ferreira,SergioT.
CognitiveNeurology&Alzheimer’sDiseaseCenter,NorthwesternUniversityInstitute
forNeuroscience,633ClarkStreet,Evanston,IL60208,USA
Klein,WilliamL.
CognitiveNeurology&Alzheimer’sDiseaseCenter,NorthwesternUniversityInstitute
forNeuroscience,633ClarkStreet,Evanston,IL60208,USA
XII Contributors
Isabel,Guillaume
GènesetDynamiquedesSystèmesdeMémoireCNRSUMR7637,ÉcoleSupérieurede
PhysiqueetChimieIndustrielle,10RueVauquelin,75005Paris,France
Lacor,PascaleN.
CognitiveNeurology&Alzheimer’sDiseaseCenter,NorthwesternUniversityInstitute
forNeuroscience,633ClarkStreet,Evanston,IL60208,USA
Lee,JonathanL.C.
DepartmentofExperimentalPsychology,MRC/WellcomeTrustBehaviouralandClin-
icalNeuroscienceInstitute,UniversityofCambridge,DowningStreet,CambridgeCB2
3EB,UK.
Miller,EarlK.
ThePicowerInstituteforLearningandMemory,RIKEN-MITNeuroscienceResearch
Center,andDepartmentofBrainandCognitiveSciences,MassachusettsInstituteof
Technology,77MassachusettsAvenue46-6241,Cambridge,MA02139,USA
Moser,EdvardI.
CentrefortheBiologyofMemory,NorwegianUniversityofScienceandTechnology,
NO-7489Trondheim,Norway
Preat,Thomas
GènesetDynamiquedesSystèmesdeMémoire,CNRSUMR7637,ÉcoleSupérieurede
PhysiqueetChimieIndustrielle,10RueVauquelin,75005Paris,France
Sargolini,Francesca
CentrefortheBiologyofMemory,NorwegianUniversityofScienceandTechnology,
NO-7489Trondheim,Norway
Silva,AlcinoJ.
DepartmentsofNeurobiology,PsychiatryandBiobehavioralSciences,Psychologyand
BrainResearchInstitute,695YoungDriveSouth,Room2357Box951761,UCLALos
Angeles,CA90095-1761,USA
Squire,LarryR.
VAMedicalCenter(116A),3350LaJollaVillageDrive,SanDiego,CA92161,USA
Suzuki,WendyA.
CenterforNeuralScience,NewYorkUniversity,BuildingMeyer,Room809,4Wash-
ingtonPlace,NewYork,NY10003,USA
Talton,LynnE.
DepartmentsofNeurobiology,PsychiatryandBiobehavioralSciences,Psychologyand
BrainResearchInstitute,695YoungDriveSouth,Room2357Box951761,UCLALos
Angeles,CA90095-1761,USA