The Small GTPase Rac1 Contributes to Extinction of Aversive Memories of Drug Withdrawal by Facilitating GABA(A) Receptor Endocytosis in the vmPFC
文献类型：期刊论文
| 作者 | Wang, Weisheng2,7; Ju, Yun-Yue2,7; Zhou, Qi-Xin1,6; Tang, Jian-Xin5; Li, Meng1,6; Zhang, Lei4; Kang, Shuo2,7; Chen, Zhong-Guo2,7; Wang, Yu-Jun2,7 ; Ji, Hui5
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| 刊名 | JOURNAL OF NEUROSCIENCE
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| 出版日期 | 2017-07-26 |
| 卷号 | 37期号:30页码:7096-7110 |
| 关键词 | aversive memory drug withdrawal endocytosis extinction GABA(A) receptor Rac1 |
| ISSN号 | 0270-6474 |
| DOI | 10.1523/JNEUROSCI.3859-16.2017 |
| 文献子类 | Article |
| 英文摘要 | Extinction of aversive memories has been a major concern in neuropsychiatric disorders, such as anxiety disorders and drug addiction. However, the mechanisms underlying extinction of aversive memories are not fully understood. Here, we report that extinction of conditioned place aversion (CPA) to naloxone-precipitated opiate withdrawal in male rats activates Rho GTPase Rac1 in the ventromedial prefrontal cortex (vmPFC) in a BDNF-dependent manner, which determines GABA(A) receptor (GABA(A)R) endocytosis via triggering synaptic translocation of activity-regulated cytoskeleton-associated protein (Arc) through facilitating actin polymerization. Active Rac1 is essential and sufficient for GABA(A)R endocytosis and CPA extinction. Knockdown of Rac1 expression within the vmPFC of rats using Rac1-shRNA suppressed GABA(A)R endocytosis and CPA extinction, whereas expression of a constitutively active form of Rac1 accelerated GABA(A)R endocytosis and CPA extinction. The crucial role of GABA(A)R endocytosis in the LTP induction and CPA extinction is evinced by the findings that blockade of GABA(A)R endocytosis by a dynamin function-blocking peptide (Myr-P4) abolishes LTP induction and CPA extinction. Thus, the present study provides first evidence that Rac1-dependent GABA(A)R endocytosis plays a crucial role in extinction of aversive memories and reveals the sequence of molecular events that contribute to learning experience modulation of synaptic GABA(A)R endocytosis. |
| WOS关键词 | MEDIAL PREFRONTAL CORTEX ; LONG-TERM POTENTIATION ; MORPHINE-DEPENDENT RATS ; IMMEDIATE-EARLY GENE ; SYNAPTIC PLASTICITY ; FEAR EXTINCTION ; BASOLATERAL AMYGDALA ; DENDRITIC SPINES ; CONDITIONED FEAR ; HIPPOCAMPAL-NEURONS |
| 资助项目 | Ministry of Science and Technology of China[2013CB835100] ; Ministry of Science and Technology of China[2015CB553502] ; Ministry of Science and Technology of China[2013CB8351003] ; Foundation of National Natural Science of China[81130087] ; Foundation of National Natural Science of China[91232716] ; Committee of Science and Technology of Shanghai[13JC140680] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000406305800006 |
| 出版者 | SOC NEUROSCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272558]  |
| 专题 | 药理学第二研究室 |
| 通讯作者 | Xu, Lin; Liu, Jing-Gen |
| 作者单位 | 1.Chinese Acad Sci, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Yunnan, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China; 3.Soochow Univ, Coll Pharmaceut Sci, KIZ SU Joint Lab Anim Model & Drug Dev, Suzhou 215123, Peoples R China; 4.Tongji Univ, Dept Anat & Neurobiol, Collaborat Innovat Ctr Brain Sci, Sch Med, Shanghai 200092, Peoples R China; 5.China Pharmaceut Univ, Dept Pharmacol, Nanjing 210009, Jiangsu, Peoples R China; 6.Chinese Acad Sci, Kunming Inst Zool, Lab Learning & Memory, Kunming 650223, Yunnan, Peoples R China; 7.Collaborat Innovat Ctr Brain Sci, Shanghai 201203, Peoples R China; 8.CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Weisheng,Ju, Yun-Yue,Zhou, Qi-Xin,et al. The Small GTPase Rac1 Contributes to Extinction of Aversive Memories of Drug Withdrawal by Facilitating GABA(A) Receptor Endocytosis in the vmPFC[J]. JOURNAL OF NEUROSCIENCE,2017,37(30):7096-7110. |
| APA | Wang, Weisheng.,Ju, Yun-Yue.,Zhou, Qi-Xin.,Tang, Jian-Xin.,Li, Meng.,...&Liu, Jing-Gen.(2017).The Small GTPase Rac1 Contributes to Extinction of Aversive Memories of Drug Withdrawal by Facilitating GABA(A) Receptor Endocytosis in the vmPFC.JOURNAL OF NEUROSCIENCE,37(30),7096-7110. |
| MLA | Wang, Weisheng,et al."The Small GTPase Rac1 Contributes to Extinction of Aversive Memories of Drug Withdrawal by Facilitating GABA(A) Receptor Endocytosis in the vmPFC".JOURNAL OF NEUROSCIENCE 37.30(2017):7096-7110. |
入库方式： OAI收割
来源：上海药物研究所
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