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The spatial and structural changes of organelles and the molecular basis underlying long-term memory consolidation

Research Project

Project/Area Number 20K06852
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 InstitutionToho University (2022)
Nagoya University (2020-2021)

Principal Investigator

AGETA-ISHIHARA Natsumi  東邦大学, 理学部, 准教授 (60547561)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords記憶 / 記憶固定 / 細胞骨格 / 可塑性 / 記憶固定化
Outline of Research at the Start

学習や記憶の細胞レベルの基盤は神経活動に応じてシナプス伝達効率が変化し、維持されるシナプス可塑性である。強い興奮性入力は樹状突起スパイン容積増加とAMPA受容体のシナプス後肥厚へのリクルートを伴うシナプス伝達の長期的な亢進(LTP)を惹起する。さらに、スパインの可塑的変化は数時間以上継続し、後期LTPをもたらす。スパインの体積増加はアクチン重合によることが支持されている一方で、数時間以上続くスパイン体積の可塑的変化に対しては、何からのメカニズムの存在が示唆されており、記憶維持に関わると考えられているが、その実体はほとんど明らかになっていない。本研究では長期記憶維持の分子基盤を解明する。

Outline of Final Research Achievements

The basis of learning and memory is long-term potentiation (LTP), which involves a long-lasting increase in transmission efficiency at the adhesion sites between neurons, and structural changes in dendritic spine. The structural changes are induced by the polymerisation of the actin cytoskeleton, but many aspects of the molecular mechanisms underlying the persistence of volume changes and electrical responses for several hours are still unclear. In this study, we have successfully presented a new concept that the movement of organelles in response to stimulation affects the maintenance of long-term memory.

Academic Significance and Societal Importance of the Research Achievements

我が国は超高齢社会を迎えており、認知症初期の時点での治療は最重要課題の一つである。臨床において、アルツハイマー病治療薬(コリンエステラーゼ阻害薬)の有効性を検討した研究があるが、根本的な治療薬は確立していない。今後は、本研究成果を認知症の治療戦略に繋ぐことを目指して、得られた基礎データに基づく、創薬や治療法の基盤となる技術開発に取り組むことを目指す。高齢化社会が進む中で基礎研究を健康寿命の延命に繋げる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (13 results)

All 2023 2022 2021 2020

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (11 results) (of which Invited: 5 results)

  • [Journal Article] Mice with cleavage-resistant N-cadherin exhibit synapse anomaly in the hippocampus and outperformance in spatial learning tasks2021

    • Author(s)
      M. Asada-Utsugi, K. Uemura, M. Kubota, Y. Noda, Y. Tashiro, T. M. Uemura, H. Yamakado, M. Urushitani, R. Takahashi, S. Hattori, T. Miyakawa, N. Ageta-Ishihara, K. Kobayashi, M. Kinoshita, A. Kinoshita
    • Journal Title

      Molecular Brain

      Volume: 14 Issue: 1 Pages: 23-23

    • DOI

      10.1186/s13041-021-00738-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Developmental and postdevelopmental roles of septins in the brain2020

    • Author(s)
      Ageta-Ishihara Natsumi、Kinoshita Makoto
    • Journal Title

      Neuroscience Research

      Volume: S0168-0102(20) Issue: 20 Pages: 30440-30445

    • DOI

      10.1016/j.neures.2020.08.006

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 記憶固定化の新たなシナプス制御機構の解明2023

    • Author(s)
      上田(石原)奈津実, 木下専
    • Organizer
      生理研研究会「ナノ・メゾスケールから捉えるシナプス制御機構の新展開」
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 記憶におけるスパイン内オルガネラの新たな役割2022

    • Author(s)
      上田(石原)奈津実
    • Organizer
      第4回三融会・武田神経科学シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Activity-triggered extension of endoplasmic reticulum into dendritic spines as a synaptic basis of memory consolidation2022

    • Author(s)
      Ageta-Ishihara N, Fukazawa Y, Kosaka Y, Mizukami M, Takao K, Kengaku M, Miyakawa T, Inokuchi K, Bito H, Kinoshita M
    • Organizer
      Neuro2022
    • Related Report
      2022 Annual Research Report
  • [Presentation] The pivotal septin subunit SEPT7 localizes to pre-/post-/peri-synaptic membrane domains and interacts with MYH10/nonmuscle myosin IIB2022

    • Author(s)
      Kinoshita M, Mitsui R, Suzuki A, Iwano D, Fukazawa Y, Ageta-Ishihara N, Hosokawa T.
    • Organizer
      Neuro 2022
    • Related Report
      2022 Annual Research Report
  • [Presentation] セプチン細胞骨格を介した小胞体の伸長は記憶の長期化の基盤となるポジティブフィードバックを制御する2022

    • Author(s)
      上田(石原)奈津実, 深澤有吾, 高雄啓三, 見学美根子, 宮川剛, 井ノ口馨, 尾藤晴彦, 木下専
    • Organizer
      第45回日本分子生物学会年会ワークショップ「生体膜の構造機能を制御する分子の秩序と集合機構」
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 記憶の長期化に寄与するスパイン内小胞体の役割2022

    • Author(s)
      上田(石原)奈津実, 木下専
    • Organizer
      第19回神経科学研究会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] A new kind of positive feed-back regulation via the organelle extension2021

    • Author(s)
      Ageta-Ishihara N
    • Organizer
      RIKEN BDR ‘Women and Future in Science’ Seminar
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] The coordination of septin cytoskeleton and actomyosin underlying memory consolidation2021

    • Author(s)
      Ageta-Ishihara N, Kosaka Y, Fujiwara R, Fuse N, Suzuki A, Kinoshita I, Mizukami M, Kinoshita M.
    • Organizer
      The 80th Fujihara Seminar “Molecular and cellular mechanisms of brain systems generating individuality”
    • Related Report
      2021 Research-status Report
  • [Presentation] A myosin/septin-dependent postsynaptic regulation required for memory consolidation2021

    • Author(s)
      Ageta-Ishihara N, Fukazawa Y, Takao K, Kengaku M, Miyakawa T, Inokuchi K, Bito H, Kinoshita M.
    • Organizer
      第44回 日本神経科学大会、第1回 CJK 国際会議
    • Related Report
      2021 Research-status Report
  • [Presentation] 個性の階層的理解を目指した記憶維持における分子・細胞・個体レベルでの評価系の確立2020

    • Author(s)
      上田(石原)奈津実, 木下専
    • Organizer
      「個性」創発脳第五回領域会議
    • Related Report
      2020 Research-status Report
  • [Presentation] Activity- and septin-dependent extension of smooth ER into dendritic spines as a synaptic basis of memory consolidation2020

    • Author(s)
      Kinoshita M, Ageta-Ishihara N, Fukazawa Y, Kengaku M, Takao K, Inokuchi K, Miyakawa T, Bito H.
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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