GABAergic and Cortical and Subcortical Glutamatergic Axon Terminals Contain CB1 Cannabinoid Receptors in the Ventromedial Nucleus of the Hypothalamus 英文参考文献.docVIP

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GABAergic and Cortical and Subcortical Glutamatergic Axon Terminals Contain CB1 Cannabinoid Receptors in the Ventromedial Nucleus of the Hypothalamus 英文参考文献.doc

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GABAergic and Cortical and Subcortical Glutamatergic Axon Terminals Contain CB1 Cannabinoid Receptors in the Ventromedial Nucleus of the Hypothalamus 英文参考文献

GABAergicandCorticalandSubcorticalGlutamatergic AxonTerminalsContainCB1CannabinoidReceptorsin theVentromedialNucleusoftheHypothalamus LeireReguero1,NagorePuente1,IzaskunElezgarai1,JuanMendizabal-Zubiaga1,MirenJosune Canduela1,IanireBuceta1,AlmudenaRamos1,JuanSua′rez2,FernandoRodr?′guezdeFonseca2 ,Giovanni Marsicano3,PedroGrandes1* 1DepartmentofNeurosciences,FacultyofMedicineandDentistry,BasqueCountryUniversity,Leioa,Spain,2Fundacio′nIMABIS,Ma′laga,Spain,3‘‘Endocannabinoidsand Neuroadaptation’’,INSERMU862NeuroCentreMagendie,Universite′ Bordeaux2,Bordeaux,France Abstract Background: Type-1 cannabinoid receptors (CB1R) are enriched in the hypothalamus, particularly in the ventromedial hypothalamic nucleus (VMH) that participates in homeostatic and behavioral functions including food intake. Although CB1Ractivationmodulatesexcitatoryandinhibitorysynaptictransmissioninthebrain,CB1Rcontributiontothemolecular architectureoftheexcitatoryandinhibitorysynapticterminalsintheVMHisnotknown.Therefore,theaimofthisstudywas toinvestigatetheprecisesubcellulardistributionofCB1RintheVMHtobetterunderstandthemodulationexertedbythe endocannabinoidsystemonthecomplexbraincircuitriesconvergingintothisnucleus. Methodology/PrincipalFindings:LightandelectronmicroscopytechniqueswereusedtoanalyzeCB1Rdistributioninthe VMHofCB1R-WT,CB1R-KOandconditionalmutantmicebearingaselectivedeletionofCB1Rincorticalglutamatergic(Glu- CB1R-KO)orGABAergicneurons(GABA-CB1R-KO).Atlightmicroscopy,CB1RimmunolabelingwasobservedintheVMHof CB1R-WT and Glu-CB1R-KO animals, being remarkably reduced in GABA-CB1R-KO mice. In the electron microscope, CB1R appearedinmembranesofbothglutamatergicandGABAergicterminals/preterminals.Therewasnosignificantdifference inthepercentageofCB1RimmunopositiveprofilesandCB1Rdensityinterminalsmakingasymmetricorsymmetricsynapses inCB1R-WTmice.Furthermore,theproportionofCB1Rimmunopositiveterminals/preterminalsinCB1R-WTandGlu-CB1R-KO micewasreducedinGABA-CB1R-KOmutants.CB1Rdensitywassimilari