Extrasynaptic GABAA Receptors and Tonic Inhibition in Rat Auditory Thalamus 英文参考文献.docVIP

ExtrasynapticGABAA ReceptorsandTonicInhibitionin RatAuditoryThalamus BenD.Richardson,LynneL.Ling,VictorV.Uteshev,DonaldM.Caspary* DepartmentofPharmacology,SouthernIllinoisUniversity-SchoolofMedicine,Springfield,Illinois,UnitedStatesofAmerica Abstract Background:Neuralinhibitionplaysanimportantroleinauditoryprocessingandattentionalgating.ExtrasynapticGABAA receptors (GABAAR),containing a4anddGABAARsubunits,arethoughttobeactivated byGABAspillover outsideofthe synapsefollowingreleaseresultinginatonicinhibitoryCl2currentwhichcouldaccountforupto90%oftotalinhibitionin visual and somatosensory thalamus. However, the presence of this unique type of inhibition has not been identified in auditorythalamus. Methodology/Principal Findings: The present study used gaboxadol, a partially selective potent agonist for d-subunit containing GABAA receptor constructs to elucidate the presence of extrasynaptic GABAARs using both a quantitative 3 receptor binding assay and patch-clamp electrophysiology in thalamic brain slices. Intense [ H]gaboxadol binding was found to be localized to the MGB while whole cell recordings from MGB neurons in the presence of gaboxadol demonstratedtheexpressionofd-subunitcontainingGABAARscapableofmediatingatonicinhibitoryCl2current. Conclusions/Significance: Potent tonic inhibitory GABAAR responses mediated by extrasynaptic receptors may be importantinunderstandinghowacousticinformationisprocessedbyauditorythalamicneuronsasitascendstoauditory cortex. In addition to affecting cellular behavior and possibly neurotransmission, functional extrasynaptic d-subunit containing GABAARs may represent a novel pharmacological target for the treatment of auditory pathologies including temporalprocessingdisordersortinnitus. Citation:RichardsonBD,LingLL,UteshevVV,CasparyDM(2011)ExtrasynapticGABAAReceptorsandTonicInhibitioninRatAuditoryThalamus.PLoSONE6(1): e16508.doi:10.1371/journal.pone.0016508 Editor:StevenBarnes,DalhousieUniversity,Canada ReceivedOctober26,2010;A