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A developmental switch in short-term synaptic plasticiy

Research Project

Project/Area Number 20K06906
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46030:Function of nervous system-related
Research InstitutionGunma University

Principal Investigator

Hosoi Nobutake  群馬大学, 大学院医学系研究科, 准教授 (90543570)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsshort-term plasticity / inhibitory synapse / cerebellum / 短期シナプス可塑性 / 発達 / 遺伝子発現解析
Outline of Research at the Start

生後大人になっていく間に、脳・神経系は形態が変わっていくだけでなく、機能的な面でもダイナミックに変化していき成熟していく。脳の神経細胞は、「シナプス」と呼ばれるつなぎ目のところで他の神経細胞に信号を伝えている。その「シナプス」を介して相手先の神経細胞の活動を適切に抑える信号を伝える「抑制性のシナプス伝達」が、成長・発達に伴い、その抑制の仕方を大きく変化させ、成熟すると相手先の神経細胞をよりしっかりと抑制できるようになる「切換え」の現象が生じることを申請者は見出した。本研究では、遺伝子解析や神経細胞の活動を記録することにより、この抑制性シナプス伝達の性質の「切換え」が生じるメカニズムに迫る。

Outline of Final Research Achievements

During development, the central nervous system changes dynamically and matures in terms of size, morphology and function. Properties of inhibitory synaptic transmission also changes dynamically and my preliminary study suggests that short-term depression switches to short-term facilitation at cerebellar inhibitory synapses during development. This implies that efficiency of synaptic inhibition improves greatly during maturation. The mechanism of this developmental switch of short-term plasticity, however, remains to be elucidated. In this study, I tried to examine the mechanism experimentally.

Academic Significance and Societal Importance of the Research Achievements

神経系における抑制性シナプス伝達の機能的発達は、いまだわかってないことも多く、また、抑制性シナプス伝達の機能不全は、自閉症や統合失調症、てんかんなどの精神疾患にも大きく関与することが知られている。したがって、本研究での成果は、今後、抑制性シナプス伝達を原因とする多くの精神疾患などの原因解明にもつながりうるし、治療方法の開発にも寄与しうると考えられる。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (16 results)

All 2023 2022 2021 2020 Other

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Elucidating the Mechanisms of Life using Patchclamp Technique and Live Imaging2023

    • Author(s)
      細井延武
    • Journal Title

      The Kitakanto Medical Journal

      Volume: 73 Issue: 3 Pages: 225-226

    • DOI

      10.2974/kmj.73.225

    • ISSN
      1343-2826, 1881-1191
    • Year and Date
      2023-08-01
    • Related Report
      2023 Annual Research Report
  • [Journal Article] Interaction between Teneurin-2 and microtubules via EB proteins provides a platform for GABAA receptor exocytosis2023

    • Author(s)
      Ichinose Sotaro、Susuki Yoshihiro、Hosoi Nobutake、Kaneko Ryosuke、Ebihara Mizuho、Hirai Hirokazu、Iwasaki Hirohide
    • Journal Title

      eLife

      Volume: 12

    • DOI

      10.7554/elife.83276

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term depression?inductive stimulation causes long-term potentiation in mouse Purkinje cells with a mutant thyroid hormone receptor2022

    • Author(s)
      Ninomiya Ayane、Amano Izuki、Kokubo Michifumi、Takatsuru Yusuke、Ishii Sumiyasu、Hirai Hirokazu、Hosoi Nobutake、Koibuchi Noriyuki
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 45

    • DOI

      10.1073/pnas.2210645119

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of microglia-targeting adeno-associated viral vectors as tools to study microglial behavior in vivo2022

    • Author(s)
      Okada Yukihiro、Hosoi Nobutake、Matsuzaki Yasunori、Fukai Yuuki、Hiraga Akito、Nakai Junichi、Nitta Keisuke、Shinohara Yoichiro、Konno Ayumu、Hirai Hirokazu
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 1224-1224

    • DOI

      10.1038/s42003-022-04200-3

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Electrophysiological and Imaging Analysis of GFP-Tagged Protein Kinase C γ Translocation in Cerebellar Purkinje Cells2022

    • Author(s)
      Hirai H, Fukai Y, Konno A, Hosoi N.
    • Journal Title

      Cerebellum

      Volume: - Issue: 5 Pages: 776-783

    • DOI

      10.1007/s12311-022-01384-6

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protein kinase Cγ in cerebellar Purkinje cells regulates Ca 2+-activated large-conductance K + channels and motor coordination2022

    • Author(s)
      Watanave M, Takahashi N, Hosoi N, Konno A, Yamamoto H, Yasui H, Kawachi M, Horii T, Matsuzaki Y, Hatada I, Hirai H.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 119(7) Issue: 7

    • DOI

      10.1073/pnas.2113336119

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The neurotoxic effect of lactational PFOS exposure on cerebellar functional development in male mice2022

    • Author(s)
      Ninomiya A, Mshaty A, Haijima A, Yajima H, Kokubo M, Khairinisa MA, Ariyani W, Fujiwara Y, Ishii S, Hosoi N, Hirai H, Amano I, Koibuchi N.
    • Journal Title

      Food Chem Toxicol

      Volume: 159:112751 Pages: 112751-112751

    • DOI

      10.1016/j.fct.2021.112751

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GABAergic neuron-specific whole-brain transduction by AAV-PHP.B incorporated with a new GAD65 promoter2021

    • Author(s)
      Hoshino Chiaki、Konno Ayumu、Hosoi Nobutake、Kaneko Ryosuke、Mukai Ryo、Nakai Junichi、Hirai Hirokazu
    • Journal Title

      Molecular Brain

      Volume: 14 Issue: 1 Pages: 1-18

    • DOI

      10.1186/s13041-021-00746-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Synaptic activation of protein kinase Cγ in cerebellar Purkinje cells2023

    • Author(s)
      Nobutake Hosoi, Yuuki Fukai, Ayumu Konno, Hirokazu Hirai
    • Organizer
      第13回国際放射線神経生物学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 小脳プルキンエ細胞におけるシナプス入力によって誘発されるガンマ型プロテインキナーゼCの細胞膜への移行2023

    • Author(s)
      細井延武、深井悠貴、今野歩、平井宏和
    • Organizer
      第101回日本生理学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] microRNAターゲット配列を用いたAAVによる新規なマイクログリア特異的遺伝子発現法の応用例とこの手法の神経細胞への影響について2022

    • Author(s)
      細井延武、岡田如弘、深井悠貴、平賀証人、松崎泰教、中井淳一、今野歩、平井宏和
    • Organizer
      日本生理学会大会第100回記念大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 甲状腺ホルモンシグナルによる小脳シナプス可塑性の調節メカニズム2021

    • Author(s)
      細井延武、二ノ宮彩音、小久保倫史、天野出月、平井宏和、鯉淵典之
    • Organizer
      第99回日本生理学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Deletion of class II ARFs causes tremor by disruption of Nav1.6 localization to the axon initial segment of cerebellar Purkinje cells in mice2020

    • Author(s)
      Nobutake Hosoi, Koji Shibasaki, Teiichi Furuichi, Hirokazu Hirai, Tetsushi Sadakata
    • Organizer
      FENS 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Insufficiency of class II ARFs causes tremor by impairment of Nav1.6 localization to the axon initial segment of cerebellar Purkinje cells in mice2020

    • Author(s)
      細井延武、柴崎貢志、古市貞一、平井宏和、定方哲史
    • Organizer
      生理研研究会 2020 シナプス研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] クラスIIARFはNav1.6を小脳プルキンエ細胞の軸索初節部に局在させる新規な役割を持つ2020

    • Author(s)
      細井延武、柴崎貢志、古市貞一、平井宏和、定方哲史
    • Organizer
      第98回日本生理学会大会 Web開催
    • Related Report
      2020 Research-status Report
    • Invited
  • [Remarks] 甲状腺ホルモンが小脳機能の発達に不可欠であることを発見

    • URL

      https://www.med.gunma-u.ac.jp/news/10403

    • Related Report
      2022 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

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