Dysfunctional Behavioral Modulation of Corticostriatal Communication in the R62 Mouse Model of Huntington’s Disease 英文参考文献.docVIP

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Dysfunctional Behavioral Modulation of Corticostriatal Communication in the R62 Mouse Model of Huntington’s Disease 英文参考文献.doc

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Dysfunctional Behavioral Modulation of Corticostriatal Communication in the R62 Mouse Model of Huntington’s Disease 英文参考文献

DysfunctionalBehavioralModulationofCorticostriatal CommunicationintheR6/2MouseModelof Huntington’sDisease S.LeeHong1,2,Desire′eCossyleon3,WajeehaA.Hussain3,LaurenJ.Walker3,ScottJ.Barton1,3, GeorgeV.Rebec1,3 * 1PrograminNeuroscience,IndianaUniversity,Bloomington,Indiana,UnitedStatesofAmerica,2DepartmentofKinesiology,IndianaUniversity,Bloomington,Indiana, UnitedStatesofAmerica,3DepartmentofPsychologicalandBrainSciences,IndianaUniversity,Bloomington,Indiana,UnitedStatesofAmerica Abstract Background:InHuntington’sdisease(HD),motorsymptomsdeveloppriortothewidespreadlossofneuronsinstriatum andcerebralcortex.Theaimofthisstudywastoexaminedysfunctionalpatternsofcorticostriatalcommunicationduring spontaneouslyoccurringbehaviorsinatransgenicmousemodelofHD. Methodology/PrincipalFindings:Localfieldpotentials(LFPs)wererecordedfromtwocloselyinterconnectedareas,motor cortexanddorsalstriatum,inwild-typecontrols(WT,n=14)andawidelyusedtransgenicHDmodel(R6/2mice,n=12).All mice werebetween theages of 7–9 weeks, acritical period of motor symptom development in R6/2s. Recordings were obtained whilethemice werebehavingfreely inanopenfield. Specific LFP activitywasextracted usingtimestamps for threeincreasinglydemandingmotorbehaviors:1)resting;2)grooming;and3)activeexploration.Powerspectraldensities (PSD)wereobtainedforthecorticalandstriatalLFPsaswellascoherencelevelsandrelativephaseacrossthefrequency spectrum.Inbothbrainregions,onlyR6/2sshowedhighfrequencyLFPoscillationsduringrestandgrooming.Asbehavior increasedfromrestingtoexploring,corticostriatalsynchronyathighfrequenciesdeclinedinR6/2s,completelyoppositeto the WT pattern. R6/2s also exhibited nearly in-phase corticostriatal activity (cortex phase leads of ,5u), while the WTs consistentlyshowedcorticalphaselagsof,20uacrossallassessedbehaviors,indicatingaleadroleforstriatum. Conclusions/Significance:Ourresultsaddtogrowingevidenceforalteredcommunicationbetweencortexandstriatumin HD and suggest more generally that increasingly demandi