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Discovery and characterization of a pressure sensation and transduction (PREST) mechanism in the presynaptic terminal in the CNS.

Research Project

Project/Area Number 21K15203
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

UCAR HASAN  東京大学, ニューロインテリジェンス国際研究機構, 特任助教 (50748423)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Discontinued (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2025: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2024: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywordspresynaptic plasticity / PREST / mechanical transmission / SV mobility / Presynaptic terminal / mechanical stimulation / mechanobiology / Release probabilty / Optogenetics / iGluSnFr / FRET / Spine enlargement / Mechanosensation / Synaptic plasticity / SNARE assembly / Glutamate release
Outline of Research at the Start

Using 2-photon and STED-microscopy I will study the molecular mechanisms of our novel finding of the pressure sensation and transduction (PREST) mechanism in the presynaptic terminal in the brain.

Outline of Annual Research Achievements

I discovered a new mechanism of synaptic vesicle(SV) mobility upon mechanical stimulation of the bouton. 1)Pushing causes dispersion of the SVs in bouton 2) Pushing enhances exocytosis in high-frequency stimulation 3)Synapsin, an SV binding protein, is also dispersed upon pushing 4)A dominant negative synapsin prevents SV dispersion, the Pr-increase and SNARE assembly that normally occurs after pushing 5)Inhibition of ERK1/2 also prevents SV dispersion, the Pr-increase and SNARE assembly that normally occurs after pushing. In summary, mobilization of SVs could enhance SV replenishment (a functional connection between 1 and 2 is to be established). These effects could be mediated by ERK phosphorylation on synapsin proteins (a functional connection between 3 and 4 is to be established).

Report

(3 results)
  • 2023 Annual Research Report
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (8 results)

All 2023 2022 2021

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

  • [Journal Article] Mechanical transmission at spine synapses: Short-term potentiation and working memory2023

    • Author(s)
      Haruo Kasai, Hasan Ucar, Yuichi Morimoto, Fumihiro Eto, Hitoshi Okazaki
    • Journal Title

      Current Opinion in Neurobiology

      Volume: 80 Pages: 102706-102706

    • DOI

      10.1016/j.conb.2023.102706

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mechanical actions of dendritic-spine enlargement on presynaptic exocytosis2021

    • Author(s)
      Ucar Hasan、Watanabe Satoshi、Noguchi Jun、Morimoto Yuichi、Iino Yusuke、Yagishita Sho、Takahashi Noriko、Kasai Haruo
    • Journal Title

      Nature

      Volume: 600 Issue: 7890 Pages: 686-689

    • DOI

      10.1038/s41586-021-04125-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Forceful synapses reveal mechanical interactions in the brain.2021

    • Author(s)
      Kasai, H. & Ucar, H.
    • Journal Title

      Nature

      Volume: 600 Pages: 2021-2021

    • DOI

      10.1038/d41586-021-03516-0

    • Related Report
      2021 Research-status Report
    • Open Access / Int'l Joint Research
  • [Presentation] Mechanical actions of dendritic-spine enlargement on the presynaptic terminal & the discovery of the Pressure Sensation and Transduction (PREST) mechanism2022

    • Author(s)
      Ucar Hasan
    • Organizer
      FENS Forum 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mechanical actions of dendritic-spine enlargement and the discovery of the PREST mechanism in the presynaptic terminals in the CNS2022

    • Author(s)
      Ucar Hasan
    • Organizer
      Japan Neuroscience Society Annual Meeting 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mechanosensing of the enlargement of dendritic spines by presynaptic terminals in rat hippocampus2022

    • Author(s)
      Ucar Hasan
    • Organizer
      MBSJ 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanosensation and PREST in the presynaptic terminals2022

    • Author(s)
      Hasan Ucar, Satoshi Watanabe, Jun Noguchi, Sho Yagishita, Yuichiro Morimoto, Noriko Takahashi, Haruo Kasai
    • Organizer
      The 45th Annual Meeting of the Japan Neuroscience Society. The 65th Annual Meeting of the Japanese Society for Neurochemistry The 32nd Annual Conference of the Japanese Neural Network Society
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Presynaptic terminals can sense spine enlargement and mechanical pressure to provide stronger synaptic transmission2021

    • Author(s)
      Hasan Ucar, Satoshi Watanabe, Jun Noguchi, Sho Yagishita, Yuichiro Morimoto, Noriko Takahashi, Haruo Kasai
    • Organizer
      The 44th Annual Meeting of the Japan Neuroscience Society. The 1st CJK International Meeting
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2024-12-25  

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