Dopamine D4 Receptor Activation Increases Hippocampal Gamma Oscillations by Enhancing Synchronization of Fast-Spiking Interneurons 英文参考文献.docVIP

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Dopamine D4 Receptor Activation Increases Hippocampal Gamma Oscillations by Enhancing Synchronization of Fast-Spiking Interneurons 英文参考文献.doc

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Dopamine D4 Receptor Activation Increases Hippocampal Gamma Oscillations by Enhancing Synchronization of Fast-Spiking Interneurons 英文参考文献

DopamineD4ReceptorActivationIncreases HippocampalGammaOscillationsbyEnhancing SynchronizationofFast-SpikingInterneurons RichardAndersson,AprilJohnston,Andre′ Fisahn* NeuronalOscillationsLaboratory,KI-AlzheimerDiseaseResearchCenter,DepartmentofNeurobiology,CareSciencesandSociety,KarolinskaInstitute,Stockholm,Sweden Abstract Background: Gamma oscillations are electric activity patterns of the mammalian brain hypothesized to serve attention, sensoryperception,workingmemoryandmemoryencoding.Theyaredisruptedoralteredinschizophrenicpatientswith associatedcognitivedeficits,whichpersistinspiteoftreatmentwithantipsychotics.Becausecognitivesymptomsareacore featureofschizophreniaitisrelevanttoexploresignalingpathwaysthatpotentiallyregulategammaoscillations.Dopamine has been reported to decrease gamma oscillation power via D1-like receptors. Based on the expression pattern of D4 receptors(D4R)inhippocampus,andpharmacologicaleffectsofD4Rligandsinanimals,wehypothesizethattheyareina positiontoregulategammaoscillationsaswell. Methodology/PrincipalFindings:Toaddressthishypothesisweuserathippocampalslicesandkainate-inducedgamma oscillations.Localfieldpotentialrecordingsaswellasintracellularrecordingsofpyramidalcells,fast-spikingandnon-fast- spikinginterneuronswerecarriedout.WeshowthatD4RactivationwiththeselectiveligandPD168077increasesgamma oscillation power, which can be blocked by the D4R-specific antagonist L745,870 as well as by the antipsychotic drug Clozapine. Pyramidal cells did not exhibit changes in excitatory or inhibitory synaptic current amplitudes, but inhibitory currentsbecamemorecoherentwiththeoscillationsafterapplicationofPD168077.Fast-spiking,butnotnon-fastspiking, interneurons,increasetheiractionpotentialphase-couplingandcoherencewithregardtoongoinggammaoscillationsin responsetoD4Ractivation.AmongseveralpossiblemechanismswefoundthattheNMDAreceptorantagonistAP5also blockstheD4Rmediatedincreaseingammaoscillationpower. Conclusions/Significance: We conclude that D4R