Removal of GABAA Receptor γ2 Subunits from Parvalbumin Neurons Causes Wide-Ranging Behavioral Alterations 英文参考文献.docVIP
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Removal of GABAA Receptor γ2 Subunits from Parvalbumin Neurons Causes Wide-Ranging Behavioral Alterations 英文参考文献
RemovalofGABAA Receptorc2Subunitsfrom
ParvalbuminNeuronsCausesWide-RangingBehavioral
Alterations
ElliLeppa¨1,Anni-MaijaLinden1,OlgaY.Vekovischeva1,JeromeD.Swinny2,3,VilleRantanen4 ,Esko
Toppila5,HaraldHo¨ger6,WernerSieghart7,PeerWulff8¤a,WilliamWisden8*¤b,EsaR.Korpi1*
1Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland, 2Medical Research Council, Anatomical Neuropharmacology Unit, Department of
Pharmacology,OxfordUniversity,Oxford,UnitedKingdom,3InstituteforBiomedicalandBiomolecularSciences,SchoolofPharmacyandBiomedicalSciences,University
of Portsmouth, Portsmouth, Hampshire, United Kingdom, 4Research Programs Unit, Genome-Scale Biology, and Institute of Biomedicine, Biochemistry and
DevelopmentalBiology,UniversityofHelsinki,Helsinki,Finland,5FinnishInstituteofOccupationalHealth,Helsinki,Finland,6CoreUnitofBiomedicalResearch,Division
ofLaboratoryAnimalScienceandGenetics,MedicalUniversityVienna,Himberg,Austria,7DepartmentofBiochemistryandMolecularBiology,CenterforBrainResearch,
MedicalUniversityVienna,Vienna,Austria,8DepartmentofClinicalNeurobiology,UniversityofHeidelberg,Heidelberg,Germany
Abstract
Weinvestigatedthebehavioralsignificanceoffastsynapticinhibitionbyabc2-typeGABAAreceptorsonparvalbumin(Pv)
cells.TheGABAA receptorc2subunitgenewasselectivelyinactivatedinPv-positiveneuronsbyCre/loxPrecombination.
TheresultingPv-Dc2micewererelativelyhealthyinthefirstpostnatalweeks;butthenasCrestartedtobeexpressed,the
miceprogressivelydevelopedwide-rangingphenotypicalterationsincludinglowbodyweight,motordeficitsandtremor,
decreased anxiety levels, decreased pain sensitivity and deficient prepulse inhibition of the acoustic startle reflex and
impairedspatiallearning.Nevertheless,thedeletionwasnotlethal,andmicedidnotshowincreasedmortalityevenafter
oneyear.Autoradiographywitht-butylbicyclophosphoro[35S]thionatesuggestedanincreasedamountofGABAAreceptors
withonlyaandbsubunitsincentralnervoussystemregionsthatcontainedhighlevelsofparvalbuminneuro
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