Social Defeat Impact on Fear Extinction and Amygdala-Prefrontal Cortical Theta Synchrony in 5-HTT Deficient Mice 英文参考文献.docVIP

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Social Defeat Impact on Fear Extinction and Amygdala-Prefrontal Cortical Theta Synchrony in 5-HTT Deficient Mice 英文参考文献.doc

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Social Defeat Impact on Fear Extinction and Amygdala-Prefrontal Cortical Theta Synchrony in 5-HTT Deficient Mice 英文参考文献

SocialDefeat:ImpactonFearExtinctionandAmygdala- PrefrontalCorticalThetaSynchronyin5-HTTDeficient Mice VenuNarayanan1,RebeccaS.Heiming2,3,FriederikeJansen2,Jo¨rgLesting1,NorbertSachser2,3 ,Hans- ChristianPape1,ThomasSeidenbecher1* 1Institute of Physiology I, Westfa¨lische Wilhelms-University, Mu¨nster, Germany, 2Department of Behavioural Biology, Westfa¨lische Wilhelms-University, Mu¨nster, Germany,3OttoCreutzfeldtCenterforCognitiveandBehavioralNeuroscience,Westfa¨lische Wilhelms-University,Mu¨nster,Germany Abstract Emotions,suchasfearandanxiety,canbemodulatedbybothenvironmentalandgeneticfactors.Onegeneticfactorisfor examplethegeneticallyencodedvariationoftheserotonintransporter(5-HTT)expression.Inthiscontext,the5-HTTplaysa keyroleintheregulationofcentral5-HTneurotransmission,whichiscriticallyinvolvedinthephysiologicalregulationof emotions including fear and anxiety. However, a systematic study which examines the combined influence of environmental and genetic factors on fear-related behavior and the underlying neurophysiological basis is missing. Therefore, in this study we used the 5-HTT-deficient mouse model for studying emotional dysregulation to evaluate consequencesofgenotypespecificdisruptionof5-HTTfunctionandrepeatedsocialdefeatforfear-relatedbehaviorsand corresponding neurophysiological activities in the lateral amygdala (LA) and infralimbic region of the medial prefrontal cortex (mPFC) in male 5-HTT wild-type (+/+), homo- (2/2) and heterozygous (+/2) mice. Naive males and experienced losers(generatedinaresident-intruderparadigm)ofallthreegenotypes,unilaterallyequippedwithrecordingelectrodesin LA and mPFC, underwent a Pavlovian fear conditioning. Fear memory and extinction of conditioned fear was examined whilerecordingneuronalactivitysimultaneouslywithfear-relatedbehavior.Comparedtonaive5-HTT+/+and+/2mice,5- HTT2/2miceshowedimpairedrecallofextinction.Inaddition,5-HTT2/2and+/2experiencedlosersshoweddelayed extinctionlearningandimpairedrecallofextincti