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Correlated LM and EM analysis of cortical microcircuit remodeling during learning

Research Project

Project/Area Number 19H03336
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 46020:Anatomy and histopathology of nervous system-related
Research InstitutionNational Institute for Physiological Sciences

Principal Investigator

Kubota Yoshiyuki  生理学研究所, 脳機能計測・支援センター, 准教授 (90192567)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2022: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywords大脳皮質 / 神経回路 / リモデリング / シナプス / スパイン / 視床 / 運動学習 / 光顕電顕相関 / 光顕-電顕相関法 / 記憶 / 可塑性 / 再編成 / 光顕-電顕相関 / CLEM
Outline of Research at the Start

脳が多様な機能を実現するには、その構造基盤としての“標準回路”のみならず、様々な学習によって可塑的に変化する“動的回路”が重要である。本研究では、電子顕微鏡による大規模電顕画像3次元再構築処理法と光学顕微鏡観察法を相関させ、マウスの運動学習に伴う大脳皮質第一次運動野の神経回路のダイナミックな変化を解析する。運動学習に伴い形成される新規のシナプス入力の由来が大脳皮質錐体細胞であるか視床の神経細胞であるかを明らかにし、それぞれが運動学習時にもたらす機能を推論する。この生体から超微細構造への“シームレスイメージング”により、運動学習を可能とする神経回路のリモデリングメカニズムを明らかにする。

Outline of Final Research Achievements

We developed correlated light and electron microscopy (CLEM) with combination of in vivo imaging using two photon microscopy and large volume electron microscopy using automated tape collecting ultramicrotome (ATUM) to analyze the cortical neural microcircuit changes that occured in the M1 cortex for seed reaching task motor learning task using with forelimb. During the learning task, we observed that the secondary motor cortex (M2) → M1 neural pathway plays an important role in “motor learning” while the acquired “motor memory” is transferred to the thalamus → M1 neural pathway, indicating that neural circuit remodeling has been occurred in M1 cortex. We concluded that “synaptic connections for learning” helps in formation and maturation of “synaptic connections for memory” for the skill learning.

Academic Significance and Societal Importance of the Research Achievements

今回の研究で、脳が“学習”した事柄をいかにして“記憶”に変換していくのかについて、新たな知見を示すことができました。例えば、箸の使い方を練習すると、初めは一生懸命に指先に神経を払う必要がありますが、練習すればするほど箸使いが上手になります。そのうちに、会話したり、テレビをみたり、新聞を読んだりしながら、無意識下で箸を上手に使いこなして食事をとるようになります。このような日常の運動学習に関わる脳の学習メカニズムの解明につながる成果だと考えています。

Report

(5 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (30 results)

All 2024 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (20 results) (of which Int'l Joint Research: 5 results,  Invited: 16 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] Charitie Universitatsmedizin Berlin/Humboldt University of Berlin/Regensburg University(ドイツ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Inst Res Fundamental Sciences(イラン)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Correlative light and electron microscopic observation of calcium phosphate particles in a mouse kidney formed under a high-phosphate diet2023

    • Author(s)
      Battulga Batpurev、Shiizaki Kazuhiro、Miura Yutaka、Osanai Yasuyuki、Yamazaki Reiji、Shinohara Yoshiaki、Kubota Yoshiyuki、Hara Toru、Kuro-o Makoto、Ohno Nobuhiko
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 852-860

    • DOI

      10.1038/s41598-023-28103-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Presynaptic supervision of cortical spine dynamics in motor learning2022

    • Author(s)
      Sohn Jaerin、Suzuki Mototaka、Youssef Mohammed、Hatada Sayuri、Larkum Matthew E.、Kawaguchi Yasuo、Kubota Yoshiyuki
    • Journal Title

      Science Advances

      Volume: 8 Issue: 30

    • DOI

      10.1126/sciadv.abm0531

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anatomical and Functional Connectivity at the Dendrodendritic Reciprocal Mitral Cell-Granule Cell Synapse: Impact on Recurrent and Lateral Inhibition.2022

    • Author(s)
      Aghvami SS, Kubota Y and Egger V
    • Journal Title

      Front. Neural Circuits

      Volume: 16 Pages: 933201-933201

    • DOI

      10.3389/fncir.2022.933201

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deep learning-based point-scanning super-resolution imaging2021

    • Author(s)
      Fang L, Monroe F, Novak SW, Kirk L, Schiavon CR, Yu SB, Zhang T, Wu M, Kastner K, Latif AA, Lin Z, Shaw A, Kubota Y, Mendenhall J, Zhang Z, Pekkurnaz G, Harris K, Howard J, Manor U
    • Journal Title

      Nature Methods

      Volume: 18 Issue: 4 Pages: 406-416

    • DOI

      10.1038/s41592-021-01080-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The critical balance between dopamine D2 receptor and RGS for the sensitive detection of a transient decay in dopamine signal.2021

    • Author(s)
      Urakubo H, Yagishita S, Kasai H, Kubota Y, Ishii S
    • Journal Title

      PLoS Comput Biol

      Volume: 17 Issue: 9 Pages: e1009364-e1009364

    • DOI

      10.1371/journal.pcbi.1009364

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] UNI-EM: An Environment for Deep Neural Network-Based Automated Segmentation of Neuronal Electron Microscopic Images2019

    • Author(s)
      Urakubo Hidetoshi、Bullmann Torsten、Kubota Yoshiyuki、Oba Shigeyuki、Ishii Shin
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 19413-19413

    • DOI

      10.1038/s41598-019-55431-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 大脳皮質神経回路研究-大容量電顕画像vEM解析法による挑戦-2024

    • Author(s)
      窪田芳之、上地龍治、宮崎隆明、川口泰雄
    • Organizer
      第129回日本解剖学会学術研究集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Large volume EM with high-throughput imaging system - a trial study for marmoset cortex neural wiring2024

    • Author(s)
      Yoshiyuki Kubota
    • Organizer
      McGill Univ-NIPS Joint Symposium: New horizons in life science research using cutting-edge methodology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cortical Spine Dynamics During a Single Seed Grasp Motor Learning2024

    • Author(s)
      Yoshiyuki Kubota
    • Organizer
      Winter Conference on Brain Research
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A large volume EM data set and microcircuit analysis of neocortex2023

    • Author(s)
      Yoshiyuki Kubota
    • Organizer
      FAOPS2023
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 高スループット画像取得が可能な透過型電子顕微鏡による巨大ボリュームイメージング2023

    • Author(s)
      宮崎 隆明, カミジ ニュートン, 窪田 芳之
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 光電子相関観察法による運動学習時の大脳皮質一次運動野の神経回路変化解析2023

    • Author(s)
      窪田芳之
    • Organizer
      日本顕微鏡学会第 79 回学術講演会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Cortical Spine Dynamics and Microcircuit Remodeling during Motor Learning2023

    • Author(s)
      Yoshiyuki Kubota
    • Organizer
      The Dendrites: Molecules, Structure and Function GRC
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 大容量電子顕微鏡画像データとコネクトミクス2023

    • Author(s)
      窪田芳之、川口泰雄
    • Organizer
      第128回日本解剖学会総会・全国学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 一次運動野運動野神経回路で運動学習時に生じるリモデリング2023

    • Author(s)
      窪田芳之
    • Organizer
      第100回日本生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 2光子・共焦点顕微鏡・大容量電顕画像によるCLEMとAI assisted dense segmentationの試み2022

    • Author(s)
      窪田芳之
    • Organizer
      クラスタ/ハブダイナミズムの決定剛軟因・ハブ決定剛軟因)領域シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 大容量電顕画像撮影と深層学習アプリによるdense segmentationの試み2022

    • Author(s)
      窪田芳之
    • Organizer
      日本顕微鏡学会生体ボリュームイメージング 第6回研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 学習に伴う大脳皮質一次運動野の神経回路構築のリモデリング2022

    • Author(s)
      Yoshiyuki Kubota, Jaerin Sohn, Yasuo Kawaguchi
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 「大容量電顕画像撮影と深層学習アプリによるdense segmentationの試み」2022

    • Author(s)
      窪田芳之
    • Organizer
      第2回 中部大学 基礎生物学研究所 生理学研究所連携セミナー「AIと生命システム」
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Presynaptic control of spine dynamics for learning and memory in neocortex2021

    • Author(s)
      Jaerin Sohn, Mototaka Suzuki, Sayuri Hatada, Mohammed Youssef, Matthew E Larkum, Yasuo Kawaguchi, Yoshiyuki Kubota
    • Organizer
      EMBO | EMBL Symposium: Seeing is Believing - Imaging the Molecular Processes of Life
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 大規模電顕画像データによる脳ミクロコネクトーム2021

    • Author(s)
      窪田芳之
    • Organizer
      諸科学における大規模データと統計数理モデリング & 諸科学における大規模・多様なデータを基盤としたデータ駆動型研究の萌芽・推進のためのワークショップ
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ラットの大脳皮質細胞へのシナプス入力特性2021

    • Author(s)
      窪田芳之、畑田小百合、山口登、Alsayed A Mohamed, 田中康裕、川口泰雄
    • Organizer
      第44回日本神経科学大会/第1回CJK国際会議
    • Related Report
      2020 Annual Research Report
  • [Presentation] ラット大脳皮質の大容量電顕画像データセット撮影と自動セグメンテーション2021

    • Author(s)
      窪田芳之
    • Organizer
      日本顕微鏡学会第77回学術講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 非錐体細胞の樹状突起へのシナプス入力特性2021

    • Author(s)
      窪田芳之、川口泰雄
    • Organizer
      第126回日本解剖学会総会・全国学術集会/第98回日本生理学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 運動学習時の皮質-皮質間連絡・視床-皮質投射の神経回路再編成2021

    • Author(s)
      孫在隣、川口泰雄、窪田芳之
    • Organizer
      第126回日本解剖学会総会・全国学術集会/第98回日本生理学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 皮質-皮質間連絡・視床-皮質投射の入力依存的な運動学習時回路動態2020

    • Author(s)
      孫在隣、窪田芳之、川口泰雄
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Book] Receptor and Ion Channel Detection in the Brain2021

    • Author(s)
      Kubota Y
    • Publisher
      Springer Nature
    • ISBN
      9781071615218
    • Related Report
      2020 Annual Research Report
  • [Remarks] 「学んだ」ことが「身につく」ときの脳の変化, 運動学習で大脳皮質神経回路が変化し学習記憶が進む

    • URL

      https://www.nips.ac.jp/release/2022/07/post_486.html

    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2025-01-30  

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