Genetic Deletion of NR3A Accelerates Glutamatergic Synapse Maturation 英文参考文献.docVIP

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Genetic Deletion of NR3A Accelerates Glutamatergic Synapse Maturation 英文参考文献.doc

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Genetic Deletion of NR3A Accelerates Glutamatergic Synapse Maturation 英文参考文献

GeneticDeletionofNR3AAcceleratesGlutamatergic SynapseMaturation MaileA.Henson1*¤,RylanS.Larsen2,ShelikhaN.Lawson2,IsabelPe′rez-Otan?o5,NobukiNakanishi6, StuartA.Lipton6,BenjaminD.Philpot1,2,3,4 1Curriculum in Neurobiology, University of North Carolina, Chapel Hill, North Carolina, United States of America, 2Department of Cell and Molecular Physiology, UniversityofNorthCarolina,ChapelHill,NorthCarolina,UnitedStatesofAmerica,3NeuroscienceCenter,UniversityofNorthCarolina,ChapelHill,NorthCarolina,United States of America, 4Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, North Carolina, United States of America, 5Cellular Neurobiology,DepartamentodeNeurociencias,CentrodeInvestigacio′nMe′dicaAplicada(CIMA)yUniversidaddeNavarra,Pamplona,Spain,6DelE.WebbCenterfor Neuroscience,AgingandStemCellResearch,Sanford-BurnhamMedicalResearchInstitute,LaJolla,California,UnitedStatesofAmerica Abstract Glutamatergic synapse maturation is critically dependentupon activation of NMDA-type glutamate receptors (NMDARs); however,thecontributionsofNR3Asubunit-containingNMDARstothisprocesshaveonlybeguntobeconsidered.Herewe characterizedtheexpressionofNR3AinthedevelopingmouseforebrainandexaminedtheconsequencesofNR3Adeletion onexcitatorysynapsematuration.WefoundthatNR3Aisexpressedinmanysubcellularcompartments,andduringearly development, NR3A subunits are particularly concentrated in the postsynaptic density (PSD). NR3A levels dramatically decline with age and are no longer enriched at PSDs in juveniles and adults. Genetic deletion of NR3A accelerates glutamatergic synaptic transmission, as measured by AMPAR-mediated postsynaptic currents recorded in hippocampal CA1.Consistentwiththefunctionalobservations,weobservedthatthedeletionofNR3Aacceleratedtheexpressionofthe glutamatereceptorsubunitsNR1,NR2A,andGluR1inthePSDinpostnatalday(P)8mice.Thesedatasupporttheideathat glutamatereceptorsconcentrateatsynapsesearlierinNR3A-knockout(NR3A-KO)mice.Theprecocious