التفاصيل البيبلوغرافية
| العنوان: |
The Small GTPase Racl Contributes to Extinction of Aversive Memories of Drug Withdrawal by Facilitating GABAA Receptor Endocytosis in the vmPFC. |
| المؤلفون: |
Weisheng Wang1, Yun-Yue Ju1, Qi-Xin Zhou2, Jian-Xin Tang3, Meng Li2, Lei Zhang4, Shuo Kang1, Zhong-Guo Chen3, Yu-Jun Wang1, Hui Ji3, Yu-Qiang Ding4, Lin Xu2,5,6 lxu@vip.163.com, Jing-Gen Liu1 jgliu@mail.simm.ac.cn |
| المصدر: |
Journal of Neuroscience. 7/26/2017, Vol. 37 Issue 30, p7096-7110. 15p. |
| مصطلحات موضوعية: |
*NEUROBEHAVIORAL disorders, *GUANOSINE triphosphatase, *DRUG withdrawal symptoms, *ENDOCYTOSIS, *GABA receptors, *BRAIN-derived neurotrophic factor, *PREFRONTAL cortex, *PHYSIOLOGY |
| مستخلص: |
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 Racl in the ventromedial prefrontal cortex (vmPFC) in a BDNF-dependent manner, which determines GABAA receptor (GABAAR) endocytosis via triggering synaptic translocation of activity-regulated cytoskeleton-associated protein (Arc) through facilitating actin polymerization. Active Racl is essential and sufficient for GABAAR endocytosis and CPA extinction. Knockdown of Racl expression within the vmPFC of rats using Racl -shRN A suppressed GABAAR endocytosis and CP A extinction, whereas expression of a constitutively active form of Rac 1 accelerated GABAAR endocytosis and CPA extinction. The crucial role of GABAAR endocytosis in the LTP induction and CPA extinction is evinced by the findings that blockade of GABAAR endocytosis by a dynamin function-blocking peptide (Myr-P4) abolishes LTP induction and CPA extinction. Thus, the present study provides first evidence that Racl-dependent GABAAR 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 GABAAR endocytosis. [ABSTRACT FROM AUTHOR] |
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