Excitability of jcBNST Neurons Is Reduced in Alcohol-Dependent Animals during Protracted Alcohol Withdrawal 英文参考文献.docVIP

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Excitability of jcBNST Neurons Is Reduced in Alcohol-Dependent Animals during Protracted Alcohol Withdrawal 英文参考文献.doc

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Excitability of jcBNST Neurons Is Reduced in Alcohol-Dependent Animals during Protracted Alcohol Withdrawal 英文参考文献

ExcitabilityofjcBNSTNeuronsIsReducedinAlcohol- DependentAnimalsduringProtractedAlcohol Withdrawal AttilaSzu¨cs1,2*,FulviaBerton3,4,PietroPaoloSanna3,WalterFrancesconi3 1BioCircuitsInstitute,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica,2BalatonLimnologicalResearchInstituteoftheHungarianAcademy of Sciences, Tihany, Hungary, 3Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California, United States of America, 4DepartmentofBiology,UniversityofPisa,Pisa,Italy Abstract Alcoholdependenceandwithdrawal hasbeenshowntocause neuroadaptivechanges atmultiplelevelsofthenervous system.Attheneuronlevel,adaptationsofsynapticconnectionshavebeenextensivelystudiedinanumberofbrainareas and accumulating evidence also shows the importance of alcohol dependence-related changes in the intrinsic cellular properties of neurons. At the same time, it is still largely unknown how such neural adaptations impact the firing and integrativepropertiesofneurons.Toaddresstheseproblems,here,weanalyzephysiologicalpropertiesofneuronsinthe bednucleusofstriaterminalis(jcBNST)inanimalswithahistoryofalcoholdependence.Asacomprehensiveapproach,first we measure passive and active membrane properties of neurons using conventional current clamp protocols and then analyzetheirfiringresponsesundertheactionofsimulatedsynapticbombardmentviadynamicclamp.Wefindthatmost physiologicalpropertiesasmeasuredbyDCcurrentinjectionarebarelyaffectedduringprotractedwithdrawal.However, neuronal excitability as measured from firing responses under simulated synaptic inputs with the dynamic clamp is markedlyreducedinall3typesofjcBNSTneurons.Theseresultssupporttheimportanceofstudyingtheeffectsofalcohol anddrugsofabuseonthefiringpropertiesofneuronswithdynamicclampprotocolsdesignedtobringtheneuronsintoa high conductance state. Since the jcBNST integrates excitatory inputs from the basolateral amygdala (BLA) and cortical inputsfromtheinfralimbicandtheinsularcort