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Identity and circuit functions of glia engrams

Research Project

Project/Area Number 21H02588
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Nagai Jun  国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (60892586)

Co-Investigator(Kenkyū-buntansha) 笠井 淳司  大阪大学, 大学院薬学研究科, 准教授 (40454649)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2022: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2021: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsグリア / 記憶 / 脳 / エングラム / アストロサイト / 神経 / 行動 / 回路
Outline of Research at the Start

行動変化に伴う神経活動を遺伝学的に標識し、活動パターンを再現する実験系により、行動と神経活動の因果関係が明瞭に検証できるようになった(例:記憶痕跡[エングラム]細胞)。一方、脳において神経回路と交錯して存在するグリアネットワークについては、活動パターンを捕捉し、再現する試みはなされていない。そこで本研究では、「特定の記憶でのみ活性化するグリアエングラムが存在する」という仮説を検証する。

Outline of Final Research Achievements

Experiments that genetically label neural activity associated with behavioral changes and recapitulate activity patterns have made it possible to clearly test the causal relationship between behavior and neural activity (e.g., memory trace [engram] cells). On the other hand, no attempt has been made to capture and replicate the activity patterns of the glia, which exists in the brain and interact with neural circuits. Therefore, in this study, we tested the hypothesis that there is a glial engram that is activated only in specific memories. We conduct glial engram perturbation experiments in the whole brain and specific regions based on behavior/state-specific whole-brain astrocyte activity distributions using a uniquely established whole-brain-level astrocyte activity-dependent exogenous gene expression induction system. By doing so, we clarified the correlation and causality of astrocyte activity during behavior.

Academic Significance and Societal Importance of the Research Achievements

我々の経験は脳内で情報処理され、記憶として蓄積される。脳細胞の相互作用により、記憶は形成あるいは消失するが、この詳細な細胞・分子基盤は明らかになっていない。脳細胞は神経細胞のみならず、多様なグリア細胞や血管からなっており、これら総体的な細胞ネットワークの動態と機能メカニズムを記述することは、記憶のしくみを解明し人間の心理や健康を深く理解する鍵となるばかりでなく、学習や記憶障害を持つ人々への治療法の開発が可能になり、アルツハイマー病のような病気の予防や治療に繋がる可能性がある。

Report

(3 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (10 results)

All 2022 2021

All Journal Article (1 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Specific and behaviorally consequential astrocyte Gq GPCR signaling attenuation in vivo with iβARK2021

    • Author(s)
      Nagai Jun、Bellafard Arash、Qu Zhe、Yu Xinzhu、Ollivier Matthias、Gangwani Mohitkumar R.、Diaz-Castro Blanca、Coppola Giovanni、Schumacher Sarah M.、Golshani Peyman、Gradinaru Viviana、Khakh Baljit S.
    • Journal Title

      Neuron

      Volume: 109(14) Issue: 14 Pages: 2256-2274.e9

    • DOI

      10.1016/j.neuron.2021.05.023

    • Related Report
      2021 Annual Research Report
  • [Presentation] Behavioral physiology with new perturbation and dissection tools for astrocytes.2022

    • Author(s)
      Jun Nagai
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Behavioral physiology with new perturbation and dissection tools for astrocytes.2022

    • Author(s)
      Jun Nagai
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Exploring astrocyte roles in top-down regulation of behavior.2022

    • Author(s)
      Jun Nagai
    • Organizer
      The 25th Annual Meeting of the Korean Society for Brain and Neural Sciences
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Behaviorally-specialized astrocyte ensembles.2022

    • Author(s)
      Jun Nagai
    • Organizer
      Neuro2022
    • Related Report
      2022 Annual Research Report
  • [Presentation] アストロサイトGPCRシグナルを標的とした神経変性疾患治療の可能性.2022

    • Author(s)
      Jun Nagai
    • Organizer
      第41回日本認知症学会学術集会・第37回日本老年精神医学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Synaptic reorganization by astrocytes in matured brains2021

    • Author(s)
      Jun Nagai
    • Organizer
      44th Annual Meeting of the Japan Neuroscience Society
    • Related Report
      2021 Annual Research Report
  • [Presentation] Manipulation tool developments to study behavioral consequences of astrocyte signaling in vivo2021

    • Author(s)
      Jun Nagai
    • Organizer
      The 44th Annual Meeting of the Molecular Biology Society of Japan
    • Related Report
      2021 Annual Research Report
  • [Presentation] Improved tools to dissect and manipulate astrocyte signaling: insights into cognition and emotion2021

    • Author(s)
      Jun Nagai
    • Organizer
      The 95th Annual Meeting of The Japanese Pharmacological Society
    • Related Report
      2021 Annual Research Report
  • [Presentation] Behavioral physiology with new perturbation and dissection tools for astrocytes2021

    • Author(s)
      Jun Nagai
    • Organizer
      The 99th Annual Meeting of the Physiological Society of Japan
    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-03-27  

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