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Understanding Memory Storage Mechanism through Optical Manipulation of Synaptic States

Research Project

Project/Area Number 18H02708
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 51010:Basic brain sciences-related
Research InstitutionNational Institute for Physiological Sciences

Principal Investigator

Murakoshi Hideji  生理学研究所, 脳機能計測・支援センター, 准教授 (90608142)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywordsシナプス / 光応答性分子 / 2光子蛍光顕微鏡
Outline of Final Research Achievements

Optogenetic techniques can be used to manipulate cellular activity with high spatiotemporal resolution. A widely used optogenetic tool is channelrhodopsin-2, which can be used to control neuronal activity at the cellular level. However, no optogenetic tool has been able to induce synaptic plasticity at the level of a single synapse. We have therefore developed a novel tool that enables optical manipulation of synapses. Specifically, we developed a light-activatable CaMKII by fusing CaMKIIα with the light-sensitive domain LOV2. This enabled us to activate light-activatable CaMKII in a single spine and induce long-term potentiation (LTP) in hippocampal neurons.

Academic Significance and Societal Importance of the Research Achievements

本研究では、光応答性に改変したCaMKII酵素を用いることで、生きた動物内で個々のシナプスの機能を強化することに成功した。また、本研究で開発した分子デザインは細胞内に存在する様々なタンパク質に応用が可能であるため、将来の光医療開発に繋がる画期的な成果であると考えられる。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (21 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 9 results) Remarks (2 results)

  • [Journal Article] Chronic neuronal excitation leads to dual metaplasticity in the signaling for structural long-term potentiation.2022

    • Author(s)
      Ueda HH, Nagasawa Y, Sato A, Onda M, and Murakoshi H
    • Journal Title

      Cell Reports

      Volume: 38 Issue: 1 Pages: 110153-110153

    • DOI

      10.1016/j.celrep.2021.110153

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tension sensor based on fluorescence resonance energy transfer reveals fiber diameter-dependent mechanical factors during myelination2021

    • Author(s)
      Shimizu T, Murakoshi H, Matsumoto H, Ichino K, Hattori A, Ueno S, Ishida A, ytajiri N, Hida H.
    • Journal Title

      Front Cell Neurosci

      Volume: 15 Pages: 685044-685044

    • DOI

      10.3389/fncel.2021.685044

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a Photoactivatable CaMKII for the Optical Manipulation in Single-synapses—Local Optogenetics—2021

    • Author(s)
      植田大海、長澤裕太郎、村越秀治
    • Journal Title

      Seibutsu Butsuri

      Volume: 61 Issue: 6 Pages: 374-377

    • DOI

      10.2142/biophys.61.374

    • NAID

      130008120209

    • ISSN
      0582-4052, 1347-4219
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Imaging intracellular protein interactions/activity in neurons using 2-photon fluorescence lifetime imaging microscopy.2021

    • Author(s)
      Ueda HH, Nagasawa Y, and Murakoshi H
    • Journal Title

      Neuroscience Research

      Volume: in press Pages: 00212-1

    • DOI

      10.1016/j.neures.2021.10.004

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 二光子蛍光寿命イメージングと色素タンパク質によるタンパク質間相互作用の可視化2020

    • Author(s)
      村越秀治、植田大海
    • Journal Title

      光学

      Volume: 49 Pages: 2025-2025

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Reciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTP.2019

    • Author(s)
      Saneyoshi T, Matsuno H, Suzuki A, Murakoshi H, Hedrick NG, Agnello E, O'Connell R, Stratton MM, Yasuda R, and Hayashi Y
    • Journal Title

      Neuron

      Volume: 102 Issue: 6 Pages: 11991210-11991210

    • DOI

      10.1016/j.neuron.2019.04.012

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ShadowR: a novel chromoprotein with reduced non-specific binding and improved expression in living cells2019

    • Author(s)
      Murakoshi Hideji、Horiuchi Hiroshi、Kosugi Takahiro、Onda Maki、Sato Aiko、Koga Nobuyasu、Nabekura Junichi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 12072-12072

    • DOI

      10.1038/s41598-019-48604-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rap2 and TNIK control Plexin-dependent tiled synaptic innervation in C. elegans.2018

    • Author(s)
      Chen Xi, Shibata AC, Hendi A, Kurashina M., Fortes E, Weilinger N, MacVicar B, Murakoshi H, Mizumoto K.
    • Journal Title

      eLife

      Volume: 7

    • DOI

      10.7554/elife.38801

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neuronal Synaptic Connections Organized by Small Numbers of Molecules.2018

    • Author(s)
      Murakoshi H.
    • Journal Title

      Minorities and Small Numbers from Molecules to Organisms in Biology. Springer Singapore.

      Volume: - Pages: 7-13

    • DOI

      10.1007/978-981-13-2083-5_2

    • ISBN
      9789811320828, 9789811320835
    • Related Report
      2018 Annual Research Report
  • [Journal Article] 共焦点レーザー走査顕微鏡vi.FLIM-②タイムドメイン2018

    • Author(s)
      村越秀治
    • Journal Title

      羊土社

      Volume: - Pages: 57-58

    • Related Report
      2018 Annual Research Report
  • [Presentation] Optogenetic manipulation and imaging of signaling molecules in dendritic spines of neurons.2020

    • Author(s)
      Hideji Murakoshi
    • Organizer
      UK-Japan Neuroscience Symposium
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Optical manipulation and imaging of signaling molecules in dendritic spines of neurons2019

    • Author(s)
      村越秀治
    • Organizer
      第60回日本組織細胞化学会総会・学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] シナプス内シグナル分子の光操作と分子活性イメージング2019

    • Author(s)
      村越秀治
    • Organizer
      "Chemistry for Neuroscience 2019”研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Optical manipulation and imaging of signaling molecules in dendritic spines of neurons.2019

    • Author(s)
      Hideji Murakoshi
    • Organizer
      Current Trends and Future Directions of Synapse-Circuit Plasticity Research.
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Optogenetic induction of synaptic plasticity at single synapses by photoactivatable CaMKII.2019

    • Author(s)
      Hideji Murakoshi
    • Organizer
      Cold Spring Harbor Laboratory Meeting
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Spatiotemporal manipulation and imaging of signaling molecules in neurons2019

    • Author(s)
      Hideji Murakoshi
    • Organizer
      The 50th NIPS International Symposium
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Optogenetic manipulation of CaMKII activity in synapses.2019

    • Author(s)
      Hideji Murakoshi
    • Organizer
      The 16th International Membrane Research Forum
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Optical manipulation and imaging of signaling molecules in dendritic spines of neurons2018

    • Author(s)
      村越秀治
    • Organizer
      第70回日本細胞生物学会第51回日本発生生物学会合同学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Imaging Protein Activity by 2-photon Fluorescence Lifetime Imaging Microscopy2018

    • Author(s)
      村越秀治
    • Organizer
      The 66th NIBB Conference, ABiS International Symposium
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Remarks] 生理学研究所 村越研究室

    • URL

      http://www.nips.ac.jp/multiphoton/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 村越研究室

    • URL

      http://www.nips.ac.jp/multiphoton/

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2023-03-16  

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