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Mechanism of general anesthetic action by controlling locus coeruleus using optogenetics.

Research Project

Project/Area Number 21K08943
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionNiigata University

Principal Investigator

Kurabe Miyuki  新潟大学, 医歯学系, 講師 (30635579)

Co-Investigator(Kenkyū-buntansha) 佐々木 美佳  岐阜大学, 大学院医学系研究科, 特任講師 (20774061)
上野 将紀  新潟大学, 脳研究所, 教授 (40435631)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords青斑核 / 全身麻酔薬 / パッチクランプ法 / DREADD / 光遺伝学 / パッチクランプ / 光遺伝学的手法
Outline of Research at the Start

全身麻酔薬による意識消失・維持・覚醒メカニズムには、青斑核NA/GABAニューロンの相互的な活動性変化が、深く関与しているのではないか?という問いのもと、全身麻酔の導入・維持・覚醒、一連の流れにおいて、これらのニューロンの活動が果たす機能的役割を、光遺伝学的手法を用いて解明する。
そのために、自由行動下の動物から、光遺伝学的手法を用いて、NA/GABAニューロンをそれぞれ操作することで、全身麻酔薬の作用がどのように変化するかを明らかにする。また、青斑核スライスから、パッチクランプ法と光遺伝学的手法を組み合わせることで、NA/GABAニューロンの相互的なシナプス伝達機構の詳細を明らかにする。

Outline of Final Research Achievements

The purpose of this study is to elucidate the functional role of the activities of NA/GABA neurons in the locus coeruleus and their interaction during the induction, maintenance, and arousal of general anesthesia, using optogenetic techniques.
To specifically manipulate the locus coeruleus NA neurons, Dbh-Cre mice were used, and AAVs expressing Cre-dependently ChR or ArchR were injected into the locus coeruleus. This enabled us to specifically manipulate NA neurons by exposing the locus coeruleus to specific wavelengths of light. In addition, NA neurons were identified from locus coeruleus slice preparations and patch clamp recordings were performed to examine the effects of propofol on synaptic transmission.

Academic Significance and Societal Importance of the Research Achievements

今回導入する光遺伝学的手法によってリアルタイムに目的のニューロンの活動をon/offすることが可能となる。これまでのin vitro, in vivoの実験系での問題点を克服し、無麻酔(覚醒)下動物に全身麻酔薬を投与し、リアルタイムに特定のニューロンを操作した際の機能的変化を解析することが可能となる。これらの新たなツールを組み合わせることによって、研究の幅が飛躍的に広がり、従来の知見とは異なる新たな全身麻酔薬の作用機序を見出せると考える。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (8 results)

All 2023 2022 2021

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Cerebrospinal fluid-contacting neuron tracing reveals structural and functional connectivity for locomotion in the mouse spinal cord2023

    • Author(s)
      Nakamura Yuka、Kurabe Miyuki、Matsumoto Mami、Sato Tokiharu、Miyashita Satoshi、Hoshina Kana、Kamiya Yoshinori、Tainaka Kazuki、Matsuzawa Hitoshi、Ohno Nobuhiko、Ueno Masaki
    • Journal Title

      eLife

      Volume: 12 Pages: 1-31

    • DOI

      10.7554/elife.83108

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural and functional properties of spinal dorsal horn neurons after peripheral nerve injury change overtime via astrocyte activation2022

    • Author(s)
      Kurabe Miyuki、Sasaki Mika、Furutani Kenta、Furue Hidemasa、Kamiya Yoshinori、Baba Hiroshi
    • Journal Title

      iScience

      Volume: 25 Issue: 12 Pages: 105555-105555

    • DOI

      10.1016/j.isci.2022.105555

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serotonin Plays a Key Role in the Development of Opioid-Induced Hyperalgesia in Mice2021

    • Author(s)
      Sasaki Mika、Kamiya Yoshinori、Bamba Keiko、Onishi Takeshi、Matsuda Keiichiro、Kohno Tatsuro、Kurabe Miyuki、Furutani Kenta、Yanagimura Harue
    • Journal Title

      The Journal of Pain

      Volume: - Issue: 6 Pages: 715-729

    • DOI

      10.1016/j.jpain.2020.12.008

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A mechanism of re-sedation caused by remimazolam2021

    • Author(s)
      Yamamoto Tomohiro、Kurabe Miyuki、Kamiya Yoshinori
    • Journal Title

      Journal of Anesthesia

      Volume: 6 Issue: 3 Pages: 467-468

    • DOI

      10.1007/s00540-021-02930-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] 全身麻酔時に青斑核ニューロンが果たす役割についての検討2023

    • Author(s)
      倉部美起
    • Organizer
      第70回日本麻酔科学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 痛み研究に関する電気生理学的実験手技2023

    • Author(s)
      倉部美起
    • Organizer
      生理研痛み研究会2022シンポジウム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Functional and structural changes in spinal dorsal horn neurons after peripheral nerve injury are long term regulated by astrocytes2022

    • Author(s)
      Miyuki Kurabe
    • Organizer
      Neuroscience 2022 Sandiego
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脊髄後角in vivo標本からの電気生理学的記録~臨床医の視点からの痛みメカニズムへのアプローチ~2021

    • Author(s)
      倉部美起
    • Organizer
      第43回日本疼痛学会
    • Related Report
      2021 Research-status Report
    • Invited

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Published: 2021-04-28   Modified: 2025-01-30  

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