BDNF dependent Rac1 GTPase activation in the vmPFC contributes to aversive memory extinction by Arc-mediated GABAA receptor endocytosis  

作　　者：WANG Wei-sheng JU Yun-yue WANG Yu-jun 刘景根 

机构地区：[1]Key Laboratory of Receptor Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences and Collaborative Innovation Center for Brain Science [2]中国科学院上海药物研究所

出　　处：《中国药理学与毒理学杂志》2017年第5期478-478,共1页Chinese Journal of Pharmacology and Toxicology

摘　　要：Extinction of aversive memories has been a major concern in neuropsychiatric disorders such as anxiety disorders and drug addiction. The ventromedial prefrontal cortex(vmPFC) is important for memory extinction,but the underlying mechanisms are little known. Here,we report that extinction of conditioned place aversion(CPA),a type of aversive memory associated with drug withdrawal,required activation of Rho GTPase Rac1 in the vmPFC in a brain-derived neurotrophic factor(BDNF)-dependent manner,which triggers actin polymerization via Pak1-cofilin signaling pathway,leading to synaptic localization of activity-regulated cytoskeleton-associated protein(Arc) in the vmPFC. The synaptic Arc further determines GABA_Areceptor(GABA_AR) endocytosis that is necessary and sufficient for vmP FC long-term potentiation and CPA extinction. Thus,extinction of an aversive memory associated with drug withdrawal is intriguingly controlled by Rac1-dependent GABA_AR endocytosis in the vmPFC,thereby suggesting therapeutic targets to promote extinction of the unwanted memory.Extinction of aversive memories has been a major concern in neuropsychiatric disorders such as anxiety disorders and drug addiction. The ventromedial prefrontal cortex(vmPFC) is important for memory extinction,but the underlying mechanisms are little known. Here,we report that extinction of conditioned place aversion(CPA),a type of aversive memory associated with drug withdrawal,required activation of Rho GTPase Rac1 in the vmPFC in a brain-derived neurotrophic factor(BDNF)-dependent manner,which triggers actin polymerization via Pak1-cofilin signaling pathway,leading to synaptic localization of activity-regulated cytoskeleton-associated protein(Arc) in the vmPFC. The synaptic Arc further determines GABA_Areceptor(GABA_AR) endocytosis that is necessary and sufficient for vmP FC long-term potentiation and CPA extinction. Thus,extinction of an aversive memory associated with drug withdrawal is intriguingly controlled by Rac1-dependent GABA_AR endocytosis in the vmPFC,thereby suggesting therapeutic targets to promote extinction of the unwanted memory.

关 键 词：brain-derived neurotrophic factor MEMORY GABA_A receptor 

分 类 号：R749.6[医药卫生—神经病学与精神病学]