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Understanding the roles of vasopressin neurons in the neural network of the central circadian clock

Research Project

Project/Area Number 19H03399
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 48020:Physiology-related
Research InstitutionKanazawa University

Principal Investigator

Mieda Michihiro  金沢大学, 医学系, 教授 (20296552)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Keywordsサーカディアンリズム / 体内時計 / 神経ネットワーク / 視床下部 / 遺伝子操作マウス / 光遺伝学 / 概日リズム / 視交叉上核 / 睡眠 / 遺伝子改変マウス
Outline of Research at the Start

視床下部の視交叉上核(SCN)の神経ネットワークは、概日(サーカディアン)リズムを制御する中枢時計として機能している。本研究では遺伝子改変マウスや神経生理学の最新の技術を用いて、中枢時計神経ネットワークの動作原理理解を目指す。現代社会では時差や夜間勤務、生活習慣の乱れにより、概日リズム変調は誰にでも起こりうる問題である。睡眠障害のみならず、気分障害、肥満、がん等、様々な疾患・健康障害のリスクを増大する。したがって、概日リズム発振のメカニズムを理解し、概日リズム変調の効果的な予防方法・対処方法を見つけることは、大変重要である。

Outline of Final Research Achievements

We have previously shown that vasopressin (AVP)-producing neurons are crucial for the central clock function of the suprachiasmatic nucleus (SCN). In this study, we further analyzed the function of AVP neurons. The results showed that (1) GABA released from SCN AVP neurons limits the neural activity of the SCN to the appropriate time frame on the SCN molecular clock so that mouse behavior occurs at the appropriate time, (2) AVP neurons regulate the period of rhythms of VIP and other SCN neurons to function as the primary pacemaker cells of the SCN neural network, and (3) AVP neurons in the hypothalamic paraventricular nucleus prominently promote wakefulness.

Academic Significance and Societal Importance of the Research Achievements

現代社会では時差や夜間勤務、生活習慣の乱れにより、概日(サーカディアン)リズムの変調は誰にでも起こりうる問題である。睡眠障害のみならず、気分障害、肥満・メタボリックシンドローム、がん等、様々な疾患・健康障害のリスクを増大する。したがって、概日リズム発振のメカニズムを理解し、概日リズム変調の効果的な予防方法・対処方法を見つけることは、大変重要である。本研究によりSCNが発振する概日リズムの振幅、周期、位相を決定する神経ネットワークレベルでのメカニズムが明らかになれば、特定のニューロンを操作することで中枢時計を自在に制御する技術にも繋がる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (21 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (11 results) (of which Invited: 3 results) Remarks (1 results)

  • [Int'l Joint Research] University of Wuerzburg(ドイツ)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Cell type-specific genetic manipulation and impaired circadian rhythms in ViptTA knock-in mice2022

    • Author(s)
      Peng Y, Tsuno Y, Matsui A, Hiraoka Y, Tanaka K, Horike S, Daikoku T, Mieda M
    • Journal Title

      Front Physiol

      Volume: 13 Pages: 895633-895633

    • DOI

      10.3389/fphys.2022.895633

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior2021

    • Author(s)
      Maejima Takashi、Tsuno Yusuke、Miyazaki Shota、Tsuneoka Yousuke、Hasegawa Emi、Islam Md Tarikul、Enoki Ryosuke、Nakamura Takahiro J.、Mieda Michihiro
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 6 Pages: 1-18

    • DOI

      10.1073/pnas.2010168118

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in mice2021

    • Author(s)
      Hasan Nazmul、Nagata Naoto、Morishige Jun-ichi、Islam Md Tarikul、Jing Zheng、Harada Ken-ichi、Mieda Michihiro、Ono Masanori、Fujiwara Hiroshi、Daikoku Takiko、Fujiwara Tomoko、Maida Yoshiko、Ota Tsuguhito、Shimba Shigeki、Kaneko Shuichi、Fujimura Akio、Ando Hitoshi
    • Journal Title

      Molecular Metabolism

      Volume: 49 Pages: 101202-101202

    • DOI

      10.1016/j.molmet.2021.101202

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 増大特集 脳の発振現象-基礎から臨床へ 中枢時計・視交叉上核によるサーカディアンリズム発振のメカニズム2020

    • Author(s)
      三枝理博
    • Journal Title

      BRAIN and NERVE

      Volume: 72 Issue: 11 Pages: 1143-1150

    • DOI

      10.11477/mf.1416201667

    • ISSN
      1344-8129, 1881-6096
    • Year and Date
      2020-11-01
    • Related Report
      2020 Annual Research Report
  • [Journal Article] The central circadian clock of the suprachiasmatic nucleus as an ensemble of multiple oscillatory neurons.2020

    • Author(s)
      Mieda M.
    • Journal Title

      Neurosci Res

      Volume: in press Pages: 24-31

    • DOI

      10.1016/j.neures.2019.08.003

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 概日時計と睡眠2020

    • Author(s)
      三枝理博
    • Journal Title

      生体の科学

      Volume: 71 Pages: 18-22

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Dopamine D2L Receptor Deficiency Causes Stress Vulnerability through 5-HT1A Receptor Dysfunction in Serotonergic Neurons2019

    • Author(s)
      Shioda Norifumi、Imai Yoshiki、Yabuki Yasushi、Sugimoto Wataru、Yamaguchi Kouya、Wang Yanyan、Hikida Takatoshi、Sasaoka Toshikuni、Mieda Michihiro、Fukunaga Kohji
    • Journal Title

      The Journal of Neuroscience

      Volume: 39 Issue: 38 Pages: 7551-7563

    • DOI

      10.1523/jneurosci.0079-19.2019

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] レム睡眠発現制御・情動脱力発作とナルコレプシー2019

    • Author(s)
      三枝理博
    • Journal Title

      睡眠医療

      Volume: 13 Pages: 367-373

    • Related Report
      2019 Annual Research Report
  • [Presentation] Critical roles of AVP neurons in the central circadian clock of the SCN2022

    • Author(s)
      Mieda M
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] AVP neurons of the SCN act as the principal circadian pacemaker cells in vivo2022

    • Author(s)
      Tsuno Y, Peng Y, Daikoku T, Horike S, Yamagata K, Maejima T, Mieda M
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Vasopressin neurons in the paraventricular hypothalamus promote wakefulness via lateral hypothalamic orexin neurons2022

    • Author(s)
      Islam MT, Rumpf F, Tsuno Y, Kodani S, Maejima T, Mieda M
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior.2021

    • Author(s)
      Maejima T, Tsuno Y, Miyazaki S, Tsuneoka Y, Hasegawa E, Islam MT, Enoki R, Nakamura TJ, Mieda M.
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Cellular clocks of AVP neurons regulate the cellular circadian period of VIP neurons in the mouse SCN in vivo2021

    • Author(s)
      Tsuno Y, Peng Y, Daikoku T, Horike S, Mieda M
    • Organizer
      第28回日本時間生物学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Vasopressin neurons in the paraventricular hypothalamus induce wakefulness via orexin neurons2021

    • Author(s)
      Islam MT, Rumpf F, Tsuno Y, Maejima T, Mieda M.
    • Organizer
      第98回日本生理学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 中枢時計におけるバソプレシン産生ニューロンの機能2020

    • Author(s)
      三枝理博
    • Organizer
      第27回日本時間生物学会学術大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] AVPニューロン特異的小胞GABAトランスポーターノックアウトマウスにおける視交叉上核概日リズムのインビボ解析2020

    • Author(s)
      津野祐輔、前島隆司、長谷川恵美、三枝理博
    • Organizer
      第97回日本生理学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 中枢概日時計神経ネットワークの遺伝学的解析2019

    • Author(s)
      三枝理博
    • Organizer
      第26回日本時間生物学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] AVPニューロン特異的Vgatノックアウトマウスにおける視交叉上核概日リズムのインビトロ、行動、及びインビボ解析2019

    • Author(s)
      津野祐輔、前島隆司、長谷川恵美、三枝理博
    • Organizer
      第26回日本時間生物学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] GABAergic transmission of AVP neurons regulates correctly timed output of the central circadian pacemaker of the SCN.2019

    • Author(s)
      三枝理博、長谷川恵美、津野祐輔、前島隆司
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Remarks] 体内時計のオン・オフタイマー設定機構の一端を解明

    • URL

      https://www.kanazawa-u.ac.jp/rd/88959

    • Related Report
      2020 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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