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- W2187948629 abstract "Schizophrenia may involve hypofunction of NMDA receptor (NMDAR)-mediated signaling, and alterations in parvalbumin-positive fast-spiking(FS)GABAneuronsthatmaycauseabnormalgammaoscillations.Itwasrecentlyhypothesizedthatprefrontalcortex(PFC) FSneuronactivityishighlydependentonNMDARactivationandthat,consequently,FSneurondysfunctioninschizophreniaissecondarytoNMDARhypofunction.However,NMDARsareabundantinsynapsesontoPFCpyramidalneurons;thus,akeyquestioniswhether FSneuronorpyramidalcellactivationismoredependentonNMDARs.WeexaminedtheAMPARandNMDARcontributiontosynaptic activationofFSneuronsandpyramidalcellsinthePFCofadultmice.InFSneurons,EPSCshadfastdecayandweakNMDARcontribution, whereas in pyramidal cells, EPSCs were significantly prolonged by NMDAR-mediated currents. Moreover, the AMPAR/NMDAR EPSCratiowashigherinFScells.NMDARantagonistsdecreasedEPSPsandEPSP‐spikecouplingmorestronglyinpyramidalcellsthan in FS neurons, showing that FS neuron activation is less NMDAR dependent than pyramidal cell excitation. The precise EPSP‐spike coupling produced by fast-decaying EPSCs in FS cells may be important for network mechanisms of gamma oscillations based on feedback inhibition. To test this possibility, we used simulations in a computational network of reciprocally connected FS neurons and pyramidalcellsandfoundthatbriefAMPAR-mediatedFSneuronactivationiscrucialtosynchronize,viafeedbackinhibition,pyramidal cellsinthegammafrequencyband.OurresultsraiseinterestingquestionsaboutthemechanismsthatmightlinkNMDARhypofunction toalterationsofFSneuronsinschizophrenia." @default.
- W2187948629 created "2016-06-24" @default.
- W2187948629 creator A5023721575 @default.
- W2187948629 date "2011-01-01" @default.
- W2187948629 modified "2023-09-26" @default.
- W2187948629 title "GlutamateReceptorSubtypesMediatingSynapticActivation ofPrefrontalCortexNeurons:RelevanceforSchizophrenia" @default.
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