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PKMζ调节恐惧消退的维持 PKMζisaproteinkinasethatplaysakeyroleinmaintainingthepersistenceoffearextinctionmemory.Theprocessoffearextinctioninvolvestheformationofnewmemoriesthatoverwriteorreplacetheoriginalfearassociations,leadingtoareductionoreliminationofthefearresponse.However,theretentionoffearextinctionmemoriesisknowntobefragileandsusceptibletoavarietyofenvironmentalandphysiologicalfactorsthatcandisruptorerasethesememories. ResearchhasshownthatPKMζisinvolvedinthemaintenanceoflong-termpotentiation(LTP)inthebrain,whichisatypeofsynapticplasticitythatunderlieslearningandmemory.PKMζisspecificallylocalizedtothesynapsesthatarestrengthenedduringLTP,anditregulatesthesynthesisandtraffickingofAMPAreceptors,whichareessentialforstabilizingsynapticstrength.Thus,PKMζhasbeenproposedtoactasamolecularmemorypersistorthatensuresthelongevityofLTPandrelatedformsofmemorystorage. Inthecontextoffearextinction,PKMζhasbeenfoundtoplayacriticalroleinthemaintenanceofextinctionmemoryinrodents.StudieshaveshownthatinjectionofaPKMζinhibitorintotheamygdala,abrainregionthatiscriticalforfearlearningandmemory,impairstheretentionoffearextinctionmemory.Conversely,overexpressionofPKMζintheamygdalaenhancesthepersistenceofextinctionmemoryeveninthefaceofareminderoftheoriginalfearassociation.ThesefindingssuggestthatPKMζisnecessaryandsufficientforthemaintenanceoffearextinctionmemory. Itisworthnotingthatfearextinctionisnotapermanenterasureoffearmemories,butratheranewlearningprocessthatcreatesacompetingassociationthatcanoverridetheoriginalfearresponse.Therefore,thepersistenceoffearextinctionmemoryrequiresanongoingprocessofupdatingandrefiningthenewmemorytraceovertime.Inthisrespect,recentresearchhasimplicatedtheroleofPKMζinmodulatingtheplasticityofthefearextinctioncircuitry. Forexample,studieshaveshownthatPKMζinhibitionleadstoanenhancedprocessofreconsolidation,whichistheprocessbywhichpreviouslyconsolidatedmemoriesaresusceptibletomodificationorupdatinguponretrieval.Inthiscase,PKMζinhibitionduringfearmemoryretrievalenhancest