Sleep-Deprivation Induces Changes in GABAB and mGlu Receptor Expression and Has Consequences for Synaptic Long-Term Depression 英文参考文献.docVIP

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Sleep-Deprivation Induces Changes in GABAB and mGlu Receptor Expression and Has Consequences for Synaptic Long-Term Depression 英文参考文献.doc

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Sleep-Deprivation Induces Changes in GABAB and mGlu Receptor Expression and Has Consequences for Synaptic Long-Term Depression 英文参考文献

Sleep-DeprivationInducesChangesinGABABandmGlu ReceptorExpressionandHasConsequencesforSynaptic Long-TermDepression RamakrishnaTadavarty1,PadmeshS.Rajput2,JenniferM.Wong1,UjendraKumar2*,BhagavatulaR. Sastry1* 1NeuroscienceResearchLaboratory,DepartmentofAnesthesiology,PharmacologyandTherapeutics,FacultyofMedicine,TheUniversityofBritishColumbia,Vancouver, BritishColumbia,2FacultyofPharmaceuticalSciences,TheUniversityofBritishColumbia,Vancouver,BritishColumbia Abstract Long term depression (LTD) in the CA1 region of the hippocampus, induced with a 20-Hz, 30s tetanus to Schaffer collaterals,isenhancedinsleep-deprived(SD)rats.Inthepresentstudy,weinvestigatedtheroleofmetabotropicglutamate receptors(mGluRs),c-Aminobutyricacid(GABA)Breceptors(GABAB-Rs)andN-methyl-D-asparticacidreceptors(NMDARs) 2+ intheLTDofthepopulationexcitatorypostsynapticpotential(pEPSP).TherequirementofCa fromL-andT-typevoltage- gatedcalciumchannels(VGCCs)andintracellularstoreswasalsostudied.ResultsindicatethatmGluRs,areleaseofCa 2+ fromintracellularstoresandGABAB-RsarerequiredforLTD.Interestingly,whilemGlu1Rsseemtobeinvolvedinbothshort- term depression and LTD, mGlu5Rs appear to participate mostly in LTD. CGP 55845, a GABAB-R antagonist, partially suppressedLTDinnormallysleeping(NS)rats,whilecompletelyblockingLTDinSDrats.Moreover,GS-39783,apositive allostericmodulatorforGABAB-R,suppressedthepEPSPinSD,butnotNSrats.SincebothmGluRsandGABAB-Rsseemtobe involved in the LTD, especially in SD rats, we examined if the receptor expression pattern and/or dimerization changed, using immunohistochemical, co-localization and co-immunoprecipitation techniques. Sleep-deprivation induced an increaseintheexpressionofGABAB-R1andmGlu1aRintheCA1regionofthehippocampus.Inaddition,co-localization andheterodimerizationbetweenmGlu1aR/GABAB-R1andmGlu1aR/GABAB-R2isenhancedinSDrats.Takentogether,our findingspresentanovelformofLTDsensitivetotheactivationofmGluRsandGABAB-Rs,andreveal,forthefirsttime,that sleep-deprivationind