Presynaptic NMDA Receptors Mediate IPSC Potentiation at GABAergic Synapses in Developing Rat Neocortex 英文参考文献.docVIP

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Presynaptic NMDA Receptors Mediate IPSC Potentiation at GABAergic Synapses in Developing Rat Neocortex 英文参考文献.doc

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Presynaptic NMDA Receptors Mediate IPSC Potentiation at GABAergic Synapses in Developing Rat Neocortex 英文参考文献

PresynapticNMDAReceptorsMediateIPSCPotentiation atGABAergicSynapsesinDevelopingRatNeocortex SeenaS.Mathew,JohnJ.Hablitz* DepartmentofNeurobiologyandEvelynF.McKnightBrainInstitute,UniversityofAlabamaatBirmingham,Birmingham,Alabama,UnitedStatesofAmerica Abstract Background:NMDAreceptorsaretraditionallyviewedasbeinglocatedpostsynaptically,atbothsynapticandextrasynaptic locations. However, both anatomical and physiological studies have indicated the presence of NMDA receptors located presynaptically.PhysiologicalstudiesofpresynapticNMDAreceptorsonneocorticalGABAergicterminalsandtheirpossible roleinsynapticplasticityarelacking. Methodology/PrincipalFindings:WereportherethatpresynapticNMDAreceptorsarepresentonGABAergicterminalsin developing(postnatalday(PND)12-15)butnotolder(PND21-25)ratfrontalcortex.UsingMK-801intherecordingpipette to block postsynaptic NMDA receptors, evoked and miniature IPSCs were recorded in layer II/III pyramidal cells in the presenceofAMPA/KAreceptorantagonists.BathapplicationofNMDAorNMDAreceptorantagonistsproducedincreases and decreases in mIPSC frequency, respectively. Physiologically patterned stimulation (10 bursts of 10 stimuli at 25Hz delivered at 1.25Hz) induced potentiation at inhibitory synapses in PND12-15 animals. This consisted of an initial rapid, largeincreaseinIPSCamplitudefollowedbyasignificantbutsmallerpersistentincrease.Similarchangeswerenotobserved in PND21-25 animals. When20mM BAPTA was included in the recording pipette, potentiation wasstill observed in the PND12-15groupindicatingthatpostsynapticincreasesincalciumwerenotrequired.Potentiationwasnotobservedwhen patternedstimulationwasgiveninthepresenceofD-APVortheNR2BsubunitantagonistRo25-6981. Conclusions/Significance: The present results indicate that presynaptic NMDA receptors modulate GABA release onto neocortical pyramidal cells. Presynaptic NR2B subunit containing NMDA receptors are also involved in potentiation at developingGABAergicsynapsesinratfrontalcortex.Modulationo