Dopamine Modulates Persistent Synaptic Activity and Enhances the Signal-to-Noise Ratio in the Prefrontal Cortex 英文参考文献.docVIP

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Dopamine Modulates Persistent Synaptic Activity and Enhances the Signal-to-Noise Ratio in the Prefrontal Cortex 英文参考文献.doc

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Dopamine Modulates Persistent Synaptic Activity and Enhances the Signal-to-Noise Ratio in the Prefrontal Cortex 英文参考文献

DopamineModulatesPersistentSynapticActivityand EnhancestheSignal-to-NoiseRatiointhePrefrontal Cortex SvenKroener1*,L.JudsonChandler1,PaulE.M.Phillips2,JeremyK.Seamans3 1DepartmentofNeurosciences,MedicalUniversityofSouthCarolina,Charleston,SouthCarolina,UnitedStatesofAmerica,2DepartmentofPsychiatryandBehavioral Science,UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica,3DepartmentofPsychiatryandBrainResearchCentre,UniversityofBritishColumbia, Vancouver,BritishColumbia,Canada Abstract Background:Theimportanceofdopamine(DA)forprefrontalcortical(PFC)cognitivefunctionsiswidelyrecognized,butits mechanisms of action remain controversial. DA is thought to increase signal gain in active networks according to an inverted U dose-response curve, and these effects may depend on both tonic and phasic release of DA from midbrain ventraltegmentalarea(VTA)neurons. Methodology/Principal Findings: We used patch-clamp recordings in organotypic co-cultures of the PFC, hippocampus and VTA to study DA modulation of spontaneous network activity in the form of Up-states and signals in the form of synchronousEPSPtrains.TheseculturespossessedatonicDAlevelandstimulationoftheVTAevokedDAtransientswithin thePFC.Theadditionofhigh($1mM)concentrationsofexogenousDAtotheculturesreducedUp-statesanddiminished excitatorysynapticinputs(EPSPs)evokedduringtheDown-state.IncreasingendogenousDAviabathapplicationofcocaine also reduced Up-states. Lower concentrations of exogenous DA (0.1mM) had no effect on the up-state itself, but they selectivelyincreasedtheefficiencyofatrainofEPSPstoevokespikesduringtheUp-state.WhenthebackgroundDAwas eliminatedbydepletingDAwithreserpineandalpha-methyl-p-tyrosine,orbypreparingcorticolimbicco-cultureswithout theVTAslice,Up-statescouldbeenhancedbylowconcentrations(0.1–1mM)ofDAthathadnoeffectintheVTAcontaining cultures. Finally, in spite of the concentration-dependent effects on Up-states, exogenous DA at all but the lowest concentrationsincreasedintracellularcurre