Temporal evolution of cortical ensembles promoting remote ...

Over weeks, new brain regions and neural pathways are recruited to support memory retrieval. In line with the systems consolidation hypothesis, ... Skiptomaincontent Thankyouforvisitingnature.com.YouareusingabrowserversionwithlimitedsupportforCSS.Toobtain thebestexperience,werecommendyouuseamoreuptodatebrowser(orturnoffcompatibilitymodein InternetExplorer).Inthemeantime,toensurecontinuedsupport,wearedisplayingthesitewithoutstyles andJavaScript. Advertisement nature natureneuroscience articles article AbstractMemoriesoffearfuleventscanlastalifetime.Theprelimbic(PL)cortex,asubregionofprefrontalcortex,playsacriticalroleinfearmemoryretrievalovertime.Moststudieshavefocusedonacquisition,consolidation,andretrievalofrecentmemories,butmuchlessisknownabouttheneuralmechanismsofremotememory.Usinganewknock-inmouseforactivity-dependentgeneticlabeling(TRAP2),wedemonstratethatneuronalensemblesinthePLcortexaredynamic.PLneuronsTRAPedduringlatermemoryretrievalsaremorelikelytobereactivatedandmakelargerbehavioralcontributionstoremotememoryretrievalcomparedtothoseTRAPedduringlearningorearlymemoryretrieval.PLactivityduringlearningisrequiredtoinitiatethistime-dependentreorganizationinPLensemblesunderlyingmemoryretrieval.Finally,whileneuronsTRAPedduringearlierandlaterretrievalshavesimilarbroadprojectionsthroughoutthebrain,PLneuronsTRAPedlaterhaveastrongerfunctionalrecruitmentofcorticaltargets. 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Additionalaccessoptions: Login Learnaboutinstitutionalsubscriptions Fig.1:TRAP2designandcharacterization.Fig.2:PLactivationpatternsduringfearlearningandmemoryretrievalovertime.Fig.3:TemporalchangesinthecausalroleofTRAPedPLneuronsinremotefearmemoryretrieval.Fig.4:EffectsofinhibitingPLneuronsonremotememoryretrieval.Fig.5:Relatingwhole-brainTRAPingpatternstomemory-guidedbehavior.Fig.6:Whole-brainanalysesofnetworkinvolvingTRAPedPLneurons. Codeavailability Customcodeforaxonquantification,tSNE,andPCAanalysesareavailablefromtheauthorsuponreasonablerequest. Dataavailability Thedatathatsupportthefindingsofthisstudyareavailablefromthecorrespondingauthoruponreasonablerequest. 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AdditionalinformationPublisher’snote:SpringerNatureremainsneutralwithregardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations.IntegratedsupplementaryinformationSupplementaryFigure1TargetingstrategyforgeneratingTRAP2mice.SupplementaryFigure2TimecourseofTRAPing.a,TimelineofvisualstimulationexperimenttodetermineeffectiveTRAPingwindow.b,ExampleimagesofTRAPedcellsinprimaryvisualcortex(V1)andprimarysomatosensorycortex(S1)ofTRAP2micethatunderwentthevisualstimulationexperiment.Scalebars,100 µm.c,QuantificationofTRAPedcelldensityinTRAP2mice(V1,F(4,16) = 10.07,P = 0.0003,n = 4,4,4,5,4fordark,–6h,–3h,0h,and3hconditions,respectively);S1,F(3,6) = 1.786,P = 0.249,n = 4,3,3,4,3fordark,–6h,–3h,0h,and3hconditions,respectively).d,QuantificationoffoldchangeinTRAPedcellsinTRAP2mice(V1,F(4,17) = 10.85,P = 0.0001,n = 4,4,4,5,4fordark,–6h,–3h,0h,and3hconditions,respectively;S1,F(4,12) = 2.590,P = 0.0903n = 4,3,3,4,3fordark,–6h,–3h,0h,and3hconditions,respectively;forbothcandd,one-wayANOVAwithDunnettpost-hoctest).e–g,Analogousexperimentsandanalysesasb–d,butusingTRAP1mice.Statisticsforf,V1,F(3,6) = 12.93,P = 0.0005;S1,F(3,6) = 1.786,P = 0.2497;, = 3percondition.Forg,V1,F(3,7) = 11.16,P = 0.0047;S1,F(3,6) = 1.786,P = 0.2497,n = 3percondition.Inallplotsandstatisticaltests,nrepresentsbiologicallyindependentanimals.*P