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Molecular signaling mechanisms in basal forebrain acetylcholine neurons in the control of arousal.

Research Project

Project/Area Number 20K07732
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionHirosaki University (2022-2023)
University of Tsukuba (2020-2021)

Principal Investigator

Niwa Yasutaka  弘前大学, 医学研究科, 准教授 (40590071)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords前脳基底部 / Ntrk1 / アセチルコリン / 睡眠覚醒 / 破傷風毒 / 脳波筋電図測定
Outline of Research at the Start

私たちの行動は外界からの情報や以前の経験によって常に左右される。ものを避けるといった瞬発的な行動から、寝不足や長時間の集中による頭の疲れなど、さまざまな時間幅での制御機構が予想されるが、特にゆっくりとした情報処理・応答が神経回路の中でどのように実装されているかの研究は遅れている。本研究では、睡眠負債という言葉が示すように、ゆっくりとした情報処理・応答が特に重要である睡眠覚醒行動に注目し、その覚醒制御に重要な前脳基底部アセチルコリン神経においてどのような分子シグナルが覚醒制御におけるゆっくりとした情報処理・応答を担っているのかを明らかにする。

Outline of Final Research Achievements

In the first fiscal year, we tested whether inhibition of basal forebrain acetylcholine neurons by introduction of PHP.eB AAV through the tail vein reproduced the same sleep-wake abnormalities as inhibition in transgenic mice, but no statistically significant differences were observed. In the second and third fiscal year, we changed the course of our research and established a series of experiments including preparation of AAV expressing tetanus toxin, introduction of the virus by capillary injection, EEG and EMG measurements and confirmation of transgene expression by immunohistochemistry in the injected mice. In the middle of the third fiscal year, the project had to be suspended due to the transfer of the principal investigator to another institution. The project had to be restarted after the transfer.

Academic Significance and Societal Importance of the Research Achievements

私たちは人生のおよそ3分の1を睡眠に費やす。裏を返せば残りの3分の2は覚醒時間であるが、この間に私たちは様々な活動を行い、脳には多様な情報が入ってくる。こうした情報は異なる時間幅で処理されて、次の行動へと反映される。脳を中心とする神経回路上の電気信号による情報伝達は、速い覚醒制御を説明する上では有用であるが、時間~日レベルのゆっくりとした情報処理・応答をうまく説明することができない。本研究は、ゆっくりとした情報処理・応答が特定の神経回路網においてどのように行われているかの解明を試みるチャレンジングなものである。本研究によって立ち上げた実験系を用いて、今後さらなる解明が進むことが期待される。

Report

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

    (7 results)

All 2023 2020

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Structure and Function of Neuronal Circuits linking Ventrolateral Preoptic Nucleus and Lateral Hypothalamic Area.2023

    • Author(s)
      Kseniia P, Saito YC, Niwa Y, Mizuno S, Takahashi S, Hirano A, Sakurai T
    • Journal Title

      Journal of Neuroscience

      Volume: - Issue: 22 Pages: 4075-4092

    • DOI

      10.1523/jneurosci.1913-22.2023

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of circadian rhythm components in EEG/EMG data of aged mice.2023

    • Author(s)
      Masuda K, Katsuda Y, Niwa Y, Sakurai T and Hirano A
    • Journal Title

      Front. Neurosci.

      Volume: 17 Pages: 1173537-1173537

    • DOI

      10.3389/fnins.2023.1173537

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rapid method for plasmid DNA recombination (Murakami-system)2023

    • Author(s)
      Murakami AM, Yonekura M, Nagatomo K, Niwa Y, Itagaki S, Murakami M.
    • Journal Title

      MethodsX

      Volume: 10 Pages: 102167-102167

    • DOI

      10.1016/j.mex.2023.102167

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel binding site between the voltage-dependent calcium channel CaV1.2 subunit and Cavβ2 subunit discovered using a new analysis method for protein-protein interactions.2023

    • Author(s)
      Murakami AM, Nagatomo K, Miyoshi I, Itagaki S, Niwa Y, Murakami M.
    • Journal Title

      Sci Rep

      Volume: 13 Issue: 1 Pages: 13986-13986

    • DOI

      10.1038/s41598-023-41168-4

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A simple, dual direct expression plasmid system in prokaryotic and mammalian cells2023

    • Author(s)
      Murakami M, Murakami AM, Yonekura M, Miyoshi I, Itagaki S, Niwa Y.
    • Journal Title

      PNAS Nexus

      Volume: 2 Issue: 5 Pages: 1-3

    • DOI

      10.1093/pnasnexus/pgad139

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Molecular genetics of muscarinic regulation during sleep and wakefulness2020

    • Author(s)
      Yasutaka Niwa, Hirotaka Obo, Jurgen Wess, Takeshi Sakurai
    • Organizer
      JNS2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Molecular genetics of muscarinic regulation during sleep and wakefulness2020

    • Author(s)
      Yasutaka Niwa, Hirotaka Obo, Jurgen Wess, Takeshi Sakurai
    • Organizer
      FENS forum
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2025-01-30  

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