Elucidation of the brain function and the molecular mechanisms of RhoA/Rho-kinase signaling in neural circuits

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23774
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0704:Neuroscience, brain sciences, and related fields
• Research Institution: Fujita Health University (2020); Nagoya University (2019)
• Principal Investigator: Zhang Xinjian 藤田医科大学, その他部局等, 助教 (10850430)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: Rho / Rho-kinase / 脳機能 / リン酸化 / ノックアウトマウス / 行動解析

Outline of Final Research Achievements

The purpose of this study was to clarify the physiological function and the molecular mechanism of RhoA- "Rho-kinase" signaling in individuals. By using constitutively-active RhoA mutant, dominant-negative Rho-kinase mutant, or Rho-kinase knockout mice, we demonstrated that RhoA- "Rho-kinase" signaling was involved in reward-related learning and memory in dopamine D1 receptor-expressing medium spiny neurons of the nucleus accumbens. On the other hand, RhoA- "Rho-kinase" signaling was involved in aversive learning and memory in dopamine D2 receptor-expressing medium spiny neurons of the nucleus accumbens.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、側坐核のD1R-MSNにおいて、RhoA-“Rho-kinase”シグナルが報酬学習・記憶に関与すること、側坐核のD2R-MSNにおいて、RhoA-“Rho-kinase”シグナルが忌避学習・記憶に関与することを明らかにした。本研究のようなアプローチで細胞内シグナル伝達機構を解明することによって、報酬記憶と関連する薬物依存症や恐怖記憶と関連するPTSDのような精神疾患の新たな治療ターゲットの発見に繋がると考えられる。