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Understanding mechanisms for synchronous and asynchronous release of neurotransmitters at central synapses

Research Project

Project/Area Number 18K06472
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionDoshisha University

Principal Investigator

Miki Takafumi  同志社大学, 研究開発推進機構, 准教授 (10598577)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywordsシナプス / シナプス小胞 / 神経伝達物質放出 / 神経伝達
Outline of Final Research Achievements

Synchronous and asynchronous release of neurotransmitters at synapses play important roles in information processing in the central nervous systems. However the mechanism for synchronous and asynchronous release remains elusive. In this study, we constructed a release model to explain temporal patterns of vesicular events upon action potentials, based on quantitative analysis of the number of released vesicles detected by the deconvolution method. From the results of the model simulation, we proposed that synaptic vesicles transit through recycling pool, replacement site and docking site before exocytosis, and that synchronous release derives from the vesicles located at docking and replacement site before an action potential arriving at presynaptic terminals, while asynchronous release derives from the vesicles located in recycling pool.

Academic Significance and Societal Importance of the Research Achievements

本研究では、脳神経伝達を担う伝達物質放出の同期・非同期性放出パターンを説明する統一的な数理モデルを提唱した。同期性放出は、速く正確な神経伝達に必須である。一方、非同期性放出は持続的な神経伝達を担う。このような異なる特徴と生理的意義を持つ神経伝達を統一したモデルで理解できたことは、これまで様々な説により理解されてきた中枢シナプスの多様なシナプス特性を一般化して理解することにつながり学術的に意義深い。またこの同期・非同期性放出パターン異常は神経疾患との関連も示唆されており、今後シナプス機能改善といった疾患治療に向けた応用研究への足掛かりになる可能性がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (4 results) Remarks (2 results)

  • [Int'l Joint Research] Paris Descartes(フランス)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Paris Descartes(フランス)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Max Plank Institute(ドイツ)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Direct imaging of rapid tethering of synaptic vesicles accompanying exocytosis at a fast central synapse2020

    • Author(s)
      Miki Takafumi、Midorikawa Mitsuharu、Sakaba Takeshi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 25 Pages: 14493-14502

    • DOI

      10.1073/pnas.2000265117

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Incomplete vesicular docking limits synaptic strength under high release probability conditions.2020

    • Author(s)
      Malagon G., Miki T., Tran V., Gomez G., Marty A.
    • Journal Title

      eLife

      Volume: 9

    • DOI

      10.7554/elife.52137

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] What we can learn from cumulative numbers of vesicular release events2019

    • Author(s)
      Miki T.
    • Journal Title

      Front. Cell Neurosci.

      Volume: 13 Pages: 257-257

    • DOI

      10.3389/fncel.2019.00257

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ca-dependence of synaptic vesicle exocytosis and endocytosis at the hippocampal mossy fibre terminal2019

    • Author(s)
      Miyano R., Miki T., Sakaba T.
    • Journal Title

      J. Physiol.

      Volume: 597 Issue: 16 Pages: 4373-4386

    • DOI

      10.1113/jp278040

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Two-component latency distributions indicate two-step vesicular release at simple glutamatergic synapses2018

    • Author(s)
      Takafumi Miki, Yukihiro Nakamura, Gerardo Malagon, Erwin Neher, Alain Marty Alain
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 3943-3943

    • DOI

      10.1038/s41467-018-06336-5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 小脳苔状線維シナプスにおけるシナプス小胞の高速動員メカニズム解明2021

    • Author(s)
      三木崇史
    • Organizer
      第98回 日本生理学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] シナプス機能を規定する分子2020

    • Author(s)
      三木崇史
    • Organizer
      第43回 日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 小脳苔状線維シナプスにおけるシナプス小胞動態の解析2019

    • Author(s)
      三木崇史
    • Organizer
      日本神経科学大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Two-component release latency distributions during presynaptic action potential trains at simple synapses2018

    • Author(s)
      Takafumi Miki, Yukihiro Nakamura, Gerardo Malagon, Isabel Llano, Erwin Neher, Alain Marty
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Research-status Report
  • [Remarks] シナプス分子機能部門 三木崇史 准教授の論文がPNAS誌に掲載

    • URL

      https://brainscience.doshisha.ac.jp/news/2020/0609/news-detail-203.html

    • Related Report
      2020 Annual Research Report
  • [Remarks]

    • URL

      https://brainscience.doshisha.ac.jp/news/2019/0624/news-detail-177.html

    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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