Endocannabinoids Differentially Modulate Synaptic Plasticity in Rat Hippocampal CA1 Pyramidal Neurons 英文参考文献.docVIP

EndocannabinoidsDifferentiallyModulateSynaptic PlasticityinRatHippocampalCA1PyramidalNeurons Jian-YiXu,RongqingChen,JianZhang,ChuChen* NeuroscienceCenterofExcellence,SchoolofMedicine,LouisianaStateUniversityHealthSciencesCenter,NewOrleans,Louisiana,UnitedStatesofAmerica Abstract Background:HippocampalCA1pyramidalneuronsreceivetwoexcitatoryglutamatergicsynapticinputs:theirmostdistal dendriticregionsinthestratumlacunosum-moleculare(SLM)areinnervatedbytheperforantpath(PP),originatingfrom layerIIIoftheentorhinalcortex,whiletheirmoreproximalregionsoftheapicaldendritesinthestratumradiatum(SR)are innervated by the Schaffer-collaterals (SC), originating from hippocampal CA3 neurons. Endocannabinoids (eCBs) are naturally occurring mediators capable of modulating both GABAergic and glutamatergic synaptic transmission and plasticityviatheCB1receptor.PreviousworkoneCBmodulationofexcitatorysynapsesintheCA1regionlargelyfocuseson the SC pathway. However, little information is available on whether and how eCBs modulate glutamatergic synaptic transmissionandplasticityatPPsynapses. Methodology/Principal Findings: By employing somatic and dendritic patch-clamp recordings, Ca2+ uncaging, and immunostaining, we demonstrate that there are significant differences in low-frequency stimulation (LFS)- or DHPG-, an agonistofgroupImetabotropicglutamatereceptors(mGluRs),inducedlong-termdepression(LTD)ofexcitatorysynaptic transmission between SC and PP synapses in the same pyramidal neurons. These differences are eliminated by pharmacologicalinhibitionwithselectiveCB1receptorantagonistsorgeneticdeletionoftheCB1receptor,indicatingthat thesedifferenceslikelyresultfromdifferentialmodulationviaaCB1receptor-dependentmechanism.Wealsorevealedthat depolarization-induced suppression of excitation (DSE), a form of short-term synaptic plasticity, and photolysis of caged 2+ Ca -inducedsuppressionofExcitatorypostsynapticcurrents(EPSCs)werelessatthePPthanthatattheSC.Inaddition, applicationofWIN55212(WIN)ind