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Mechanisms and significance of GABAergic synaptic deinhibition in motor learning

Research Project

Project/Area Number 21K11168
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59010:Rehabilitation science-related
Research InstitutionYamaguchi University

Principal Investigator

Kida Hiroyuki  山口大学, 大学院医学系研究科, 講師 (70432739)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords運動学習 / GABA / スパイン / AMPA受容体 / GABA受容体 / シナプス可塑性 / GABA抑制 / layerV / 脱抑制
Outline of Research at the Start

運動障害に対するリハビリテーションや効率の良い運動学習の確立には、大脳皮質一次運動野(M1)におけるシナプス可塑性メカニズム解明が必要である。申請者は、これまでの研究から運動トレーニング直後、M1の各層においてAMPA受容体を介した興奮性シナプス強化とともにGABA応答が減弱する「脱抑制」によってシナプス伝達効率が亢進していることを発見した。本研究では、光遺伝学的手法を用いて、M1内の抑制性細胞の活動を制御し、運動学習時におけるGABA脱抑制の意義を明らかにする。

Outline of Final Research Achievements

Activity-dependent plasticity in the brain is the neural basis of learning and is also involved in skill learning in the primary motor cortex (M1). To elucidate the mechanism of synaptic plasticity in layer V, we conducted electrophysiological experiments, spine observations using two photon microscopy, and quantitative evaluation of acetylcholine secretion using microdialysis. An increase in spine head was observed immediately after motor learning, along with disinhibition that decreased the frequency of miniature inhibitory postsynaptic currents. Furthermore, a significant correlation between acetylcholine and motor scores was observed.

Academic Significance and Societal Importance of the Research Achievements

AChによる興奮性活動の上昇はM1ニューロンのスパイン可塑性を含めた神経可塑性を誘発するトリガーとなると考えられる。本研究により、M1のV層における細胞特異的なシナプス可塑性様式および、アセチルコリンの役割が明らかになった。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (7 results)

All 2024 2023 2022

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (4 results)

  • [Journal Article] Development of implantable devices for epilepsy: research with cats, dogs, and macaques in biomedical engineering2024

    • Author(s)
      Sayuki Takara, Hiroyuki Kida, Takao Inoue
    • Journal Title

      ADVANCED ROBOTICS

      Volume: in press

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Motor training promotes both synaptic and intrinsic plasticity of layer V pyramidal neurons in the primary motor cortex.2023

    • Author(s)
      Kida H, Kawakami R, Sakai K, Otaku H, Imamura K, Han-Thiri-Zin, Sakimoto Y, Mitsushima D.
    • Journal Title

      The Journal of Physiology

      Volume: 601(2) Issue: 2 Pages: 335-353

    • DOI

      10.1113/jp283755

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] A critical period for learning and plastic changes at hippocampal CA1 synapses.2022

    • Author(s)
      Sakimoto Y, Matsumoto A, Yoshiura D, Goshima M, Kida H, Mitsushima D.
    • Journal Title

      Scientific Reports

      Volume: in press

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Dynamics of synaptic plasticity and acetylcholine secretion in layer V neurons of primary motor cortex by motor learning2023

    • Author(s)
      木田裕之
    • Organizer
      第101回日本生理学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Motor training promotes both synaptic and intrinsic plasticity of layer V pyramidal neurons in the primary motor cortex2023

    • Author(s)
      木田裕之
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 運動学習におけるV層細胞のシナプス可塑性2023

    • Author(s)
      木田 裕之, 川上 良介, 﨑本 裕也, 美津島 大
    • Organizer
      第100回 日本生理学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 一次運動野におけるスキル学習の神経基盤2022

    • Author(s)
      木田 裕之
    • Organizer
      第128回山口大学医学会学術講演会
    • Related Report
      2022 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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