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Learning and Long-term Memory

開催日 2014/9/11
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Prefrontal dopamine controls fear reinstatement through the inactivation of extinction circuits

  • P1-277
  • 今村(人羅) 菜津子 / Natsuko Imamura (hitora):1 野村 洋 / HIROSHI NOMURA:1 三浦 友樹 / YUKI MIURA:1 手代木 知恵 / CHIE TESHIROGI:1 松木 則夫 / NORIO MATSUKI:1 池谷 裕二 / YUJI IKEGAYA:1,2 
  • 1:東京大院・薬・薬品作用 / Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan 2:脳情報通信融合研究センター / Center for Information and Neural Networks, Osaka, Japan 

Prevention of relapses is a major challenge in treating anxiety disorders. Elucidation of the mechanisms underlying fear reinstatement will lead to the development of effective interventions for relapse. In this study, we investigated the neural circuits for fear reinstatement. Mice received footshocks in a conditioning chamber and were re-exposed to the chamber without shocks to extinguish fear. A single weak shock, a reminder shock, reinstated the once extinguished conditioned fear. c-Fos immunostaining study revealed that, with fear reinstatement, neuronal activities decreased in the infralimbic cortex (IL) and the intercalated amygdala neurons (ITC), which are brain regions crucial for fear extinction. On the other hand, neuronal activity increased in the medial subdivision of the central nucleus of the amygdala (CeM), which is necessary for fear expression. Microinjection of an NMDA receptor antagonist AP5 into the IL before the reminder shock blocked the activity change in the ITC and CeM and fear reinstatement. Notably, we identified IL dopamine as a central regulator. A reminder shock activated IL-projecting dopaminergic neurons in the ventral tegmental area, and microinjection of a dopamine D1 receptor antagonist SCH23390 into the IL before the reminder shock prevented reinstatement. These findings demonstrate that dopamine controls fear reinstatement through the inactivation of IL and ITC and the disinhibition of CeM.

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