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GABAergic Control of Critical Developmental Periods for Anxiety- and Depression-Related Behavior in Mice 英文参考文献.docVIP

GABAergic Control of Critical Developmental Periods for Anxiety- and Depression-Related Behavior in Mice 英文参考文献.doc

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GABAergic Control of Critical Developmental Periods for Anxiety- and Depression-Related Behavior in Mice 英文参考文献

GABAergicControlofCriticalDevelopmentalPeriodsfor Anxiety-andDepression-RelatedBehaviorinMice QiuyingShen1,2,4,ThomasFuchs1,4,NadiaSahir1,4,BernhardLuscher1,2,3,4 * 1Department of Biology, Pennsylvania State University, University Park, Pennsylvania, United States of America, 2Department of Biochemistry Molecular Biology, Pennsylvania StateUniversity, UniversityPark,Pennsylvania, UnitedStatesofAmerica,3DepartmentofPsychiatry,Pennsylvania StateUniversity, CollegeofMedicine, Hershey, Pennsylvania, United States of America, 4Center for Molecular Investigation of Neurological Disorders, Pennsylvania State University, University Park, Pennsylvania,UnitedStatesofAmerica Abstract Vulnerabilityforanxietyanddepressivedisordersisthoughttohaveoriginsinearlylifeandisincreasinglyrecognizedto involvedeficitsinGABAergicneurotransmission.Micethatwererenderedheterozygousforthec2subunitgeneofGABAA receptors(GABAARs)showbehavioral,cognitive,neuroendocrineandpharmacologicfeaturesexpectedofamousemodel ofmelancholicanxiousdepression,includingreducedsurvivalofadult-bornhippocampalneurons.Hereweembarkedon elucidatingthedevelopmentalsubstrateunderlyingthisphenotype,focusingontheElevatedPlusMazeandForcedSwim Test as relevant behavioral paradigms. In a first series of experiments using hemizygous tamoxifen-induced genetic inactivationofafloxedc2genomiclocusweshowthatreducingthegenedosageatpostnataldays(P)13/14butnotP27/28 resultsinalteredbehaviorinbothofthesetestsinadulthood,reminiscentoftheanxious-depressivephenotypepreviously describedforglobalheterozygousmice.However,incontrasttoglobalheterozygousmice,thebehavioralchangesinduced byc2subunitknockdownatP13/14occurredwithoutchangesinadulthippocampalneurogenesis,indicatingthataltered neurogenesisisnotanabsoluteprerequisiteforanxiety-anddepression-relatedbehaviorinthismodel.Inaseparateseries ofexperimentsusingapharmacologicalapproach,acutebuttransientpotentiationofGABAARswithdiazepamuncovered distinctdevelopmentalvulnerabilitiesforalter

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