Optimality Model of Unsupervised Spike-Timing-Dependent Plasticity Synaptic Memory and Weig

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92:3338-3343, 2004. First published Jul 7, 2004; doi:10.1152/jn.00376.2004 J NeurophysiolPer Jesper Sjöström, Gina G. Turrigiano and Sacha B. Nelson You might find this additional information useful...43 articles, 16 of which you can access free at: This article cites http://jn.physiology.org/cgi/content/full/92/6/3338#BIBL

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PerJesperSjo¨stro¨m,GinaG.Turrigiano,andSachaB.NelsonDepartmentofBiologyandVolenCenterforComplexSystems,BrandeisUniversity,Waltham,Massachusetts02454-9110

Submitted13April2004;acceptedinfinalform2July2004

Sjo¨stro¨m,PerJesper,GinaG.Turrigiano,andSachaB.Nelson.Endocannabinoid-dependentneocorticallayer-5LTDintheabsenceofpostsynapticspiking.JNeurophysiol92:3338–3343,2004.FirstpublishedJuly7,2004;doi:10.1152/jn.00376.2004.Long-termde-pression(LTD)wasinducedinneocorticallayer5pyramidalconnec-tionsbypairingpresynapticfiringwithsubthresholdpostsynapticdepolarization(dLTD)orviaaspike-timingprotocol(tLTD).LiketLTD,dLTDreducedshort-termdepressionandincreasedthecoeffi-cientofvariationconsistentwithapresynapticsiteofexpression.AlsoliketLTD,dLTDwasblockedbyCB1cannibinoidreceptorblockadeandrequiredactivationofpresumablypresynapticNR2B-containingN-methyl-D-aspartatereceptors.ThetwoformsofLTDhadidentical

magnitudesandtimecoursesandoccludedoneanother,andneitherdependedonfrequency.Finally,dLTDshareswithtLTDtheasym-metrictemporalwindowofinduction.Inconclusion,thetypesofLTDinducedbythesetwoprotocolsareindistinguishable,suggestingthatthemechanismthatunderliestLTDparadoxicallydoesnotrequirepostsynapticspiking:ThesubthresholdpostsynapticdepolarizationsofdLTDappeartofullysubstituteforpostsynapticspiking

INTRODUCTIONAtcentralglutamatergicsynapses,multipleformsoflong-termdepression(LTD)havebeenidentified.Theseformscanvaryinwhethertheyareexpressedpresynaptically(Eggeretal.1999;Zakharenkoetal.2002)orpostsynaptically(Linden2001;WangandLinden2000)andwhethertheyrequireN-methyl-D-aspartatereceptor(NMDAR)activation(Kirk-woodandBear1994;MulkeyandMalenka1992)orCa2ϩ

entrythroughsomeothermechanism(Normannetal.2000;Wangetal.1997).Insomecases,multipleformsofLTDcanoccuratthesamesynapses,dependingonanimalage(Kempetal.2000)orinductionprotocol(Normannetal.2000;Olietetal.1997).Recently,wedescribedanovelformofpresynapticcoinci-dencedetectionforneocorticallayer-5(L5)timing-dependentLTD(tLTD),thatdependsonthesimultaneousactivationofpresynapticNR2Bsubunit-containingNMDARsandendocan-nabinoidCB1receptors(Sjo¨stro¨metal.2003).Priorworkatvisualcorticalsynapses,however,hasinvestigatedtheproper-tiesandmechanismsofLTDusingtwootherprotocols:extra-cellularlow-frequencystimulation(LFS)(KirkwoodandBear1994)andpairingofpresynapticstimulationwithweakpostsynapticdepolarization(dLTD)(Artolaetal.1990).Here,wehavesoughttodeterminewhetherornotthemechanismsidentifiedfortLTDextendtotheLFSordLTDinductionprotocols.