NMDA Mediated Contextual Conditioning Changes miRNA Expression 英文参考文献.docVIP

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NMDA Mediated Contextual Conditioning Changes miRNA Expression 英文参考文献.doc

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NMDA Mediated Contextual Conditioning Changes miRNA Expression 英文参考文献

NMDAMediatedContextualConditioningChanges miRNAExpression MinJeongKye1,2,5,PierreNeveu1,3.,Yong-SeokLee4.,MiouZhou4,JudithA.Steen5,MustafaSahin5, KennethS.Kosik1,2*,AlcinoJ.Silva4 1Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, California, United States of America, 2Department of Molecular, Cellular and DevelopmentalBiology,UniversityofCaliforniaSantaBarbara,SantaBarbara,California,UnitedStatesofAmerica,3KavliInstituteforTheoreticalPhysics,Universityof California Santa Barbara, Santa Barbara, California, United States of America, 4Departments of Neurobiology, Psychiatry and Psychology, Brain Research Institute, IntegrativeCenterforLearningandMemory,DavidGeffenSchoolofMedicineatUniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica, 5TheF.M.KirbyNeurobiologyCenter,DepartmentofNeurology,Children’sHospitalBoston,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica Abstract Wemeasuredtheexpressionof187miRNAsusingquantitativerealtimePCRinthehippocampalCA1regionofcontextually conditioned mice and cultured embryonic rat hippocampal neurons after neuronal stimulation with either NMDA or bicuculline.ManyofthechangesinmiRNAexpressionafterthesethreetypesofstimulationweresimilar.Surprisingly,the expression level of half of the 187 measured miRNAs was changed in response to contextual conditioning in an NMDA receptor-dependent manner. Genes that control miRNA biogenesis and components of the RISC also exhibited activity inducedexpressionchangesandarelikelytocontributetothewidespreadchangesinthemiRNAprofile.Thewidespread changes in miRNA expression are consistent with the finding that genes up-regulated by contextual conditioning have longer 39 UTRs and more predicted binding sites for miRNAs. Among the miRNAs that changed their expression after contextual conditioning, several inhibit inhibitors of the mTOR pathway. These findings point to a role for miRNAs in learningandmemorythatincludesmTOR-dependentm