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Analysis of plasticity of neurotransmission in the dentate granule cell synapses

Research Project

Project/Area Number 21K19316
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 46:Neuroscience and related fields
Research InstitutionDoshisha University

Principal Investigator

Hashimotodani Yuki  同志社大学, 研究開発推進機構, 准教授 (50401906)

Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywords海馬 / シナプス可塑性 / CA3 / 苔状線維 / LTP / 膜容量測定 / 長期増強 / 歯状回
Outline of Research at the Start

シナプス伝達効率が長時間に渡って増強する長期増強(LTP)は、記憶・学習の細胞レベルの基盤と考えられている。LTPには、シナプス後部で変化する場合とシナプス前部で変化する場合がある。歯状回の顆粒細胞の軸索である苔状線維と海馬CA3錐体細胞で形成されるシナプスのシナプス前終末は、巨大な神経終末を作り、皮質内のシナプスでは例外的に、直接電気記録が可能である。しかも苔状線維―CA3シナプスはシナプス前部の変化によってLTPが起こる。本研究ではシナプス前終末からパッチクランプ法による電気記録を行うことによって、これまで未解明であったシナプス前性LTPのメカニズムを明らかにすることを目指す。

Outline of Final Research Achievements

Presynaptic long-term potentiation (LTP) is thought to play an important role in learning and memory. However, the underlying mechanism remains elusive because of the difficulty of direct recording during LTP. Hippocam- pal mossy fiber synapses exhibit pronounced LTP of transmitter release after tetanic stimulation and have been used as a model of presynaptic LTP. Here, we induced LTP by optogenetic tools and applied direct presynaptic patch-clamp recordings. The action potential waveform and evoked presynaptic Ca2+ currents remained un- changed after LTP induction. Membrane capacitance measurements suggested higher release probability of synaptic vesicles without changing the number of release-ready vesicles after LTP induction. We propose that dynamic changes in the active zone components may be relevant for the increased fusion competence and synaptic vesicle replenishment during LTP.

Academic Significance and Societal Importance of the Research Achievements

シナプス伝達効率が長時間に渡って増強する長期増強(LTP)は、記憶・学習の細胞レベルの基盤と考えられている。したがってLTPのメカニズムを細胞・分子レベルで明らかにすることは、記憶・学習の分子機構を理解するうえで極めて重要である。さらに認知症の治療やAI開発にも貢献する可能性がある。
したがってLTPの分子メカニズムを調べた本研究の成果は今後、ヒトでの応用を考慮した場合にも有用な知見を与えると期待される。

Report

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

    (9 results)

All 2023 2022 Other

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (2 results) Book (1 results) Remarks (3 results)

  • [Journal Article] Increased vesicle fusion competence underlies long-term potentiation at hippocampal mossy fiber synapses2023

    • Author(s)
      Fukaya Ryota、Hirai Himawari、Sakamoto Hirokazu、Hashimotodani Yuki、Hirose Kenzo、Sakaba Takeshi
    • Journal Title

      Science Advances

      Volume: 9 Issue: 8 Pages: 1-13

    • DOI

      10.1126/sciadv.add3616

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Subcortical glutamatergic inputs exhibit a Hebbian form of long-term potentiation in the dentate gyrus2022

    • Author(s)
      Hirai Himawari、Sakaba Takeshi、Hashimotodani Yuki
    • Journal Title

      Cell Reports

      Volume: 41 Issue: 13 Pages: 111871-111871

    • DOI

      10.1016/j.celrep.2022.111871

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Excitatory selective LTP of supramammillary glutamatergic/GABAergic cotransmission potentiates dentate granule cell firing2022

    • Author(s)
      Tabuchi Eri、Sakaba Takeshi、Hashimotodani Yuki
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 13

    • DOI

      10.1073/pnas.2119636119

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] 乳頭体上核ー歯状回顆粒細胞シナプスで誘導される NMDA 受容体依存性の長期増強2023

    • Author(s)
      橋本谷祐輝、平井向日葵、坂場武史
    • Organizer
      第100回 日本生理学大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 乳頭体上核ー歯状回顆粒細胞シナプスおける脱分極誘導性 LTP2022

    • Author(s)
      橋本谷祐輝、田淵詠梨、坂場武史
    • Organizer
      第45回 日本神経科学大会
    • Related Report
      2022 Annual Research Report
  • [Book] Exocytosis: From Molecules to Cells2022

    • Author(s)
      Takafumi Miki, Yuki Hashimotodani and Takeshi Sakaba
    • Total Pages
      372
    • Publisher
      IOP Publishing
    • Related Report
      2022 Annual Research Report
  • [Remarks] EurekAlert

    • URL

      https://www.eurekalert.org/news-releases/977915

    • Related Report
      2022 Annual Research Report
  • [Remarks] 新着ニュース

    • URL

      https://brainscience.doshisha.ac.jp/news/2023/0106/news-detail-279.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] 新着ニュース

    • URL

      https://brainscience.doshisha.ac.jp/news/2023/0302/news-detail-283.html

    • Related Report
      2022 Annual Research Report

URL: 

Published: 2021-07-13   Modified: 2024-01-30  

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