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Neural mechanisms of the central clock to integrate many component clock cells for the generation and transmission of the robust circadian rhythm

Research Project

Project/Area Number 23K24064
Project/Area Number (Other) 22H02802 (2022-2023)
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund (2024)
Single-year Grants (2022-2023)
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) 2024-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2024: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2023: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2022: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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

中枢概日時計・視交叉上核(SCN)神経ネットワークの動作原理は不明な点が多い。応募者らはこれまで、バソプレシン産生ニューロンの重要性を明らかにしてきた。本研究ではこれまでの研究で得たモデルマウスに、様々な生体内神経活動計測・操作法を適用する。このアプローチにより、中枢時計神経ネットワークが構成細胞を統合し概日リズムを発振・発信するメカニズムの理解を目指す。特定のSCNニューロンの操作により中枢時計を整調する技術など、概日リズム変調に関連する疾患・健康障害への効果的な対処法の発明につながる。

Outline of Final Research Achievements

The neural mechanism underlying the central circadian clock of the suprachiasmatic nucleus (SCN) is still unclear. By applying various in vivo methods to measure and manipulate neural activity in mouse models from previous studies, we sought to understand the mechanisms by which the central clock neural network generates and transmits the robust circadian rhythm. We obtained several interesting results, including that AVP neurons function as the primary pacesetter cells of the SCN, and that the neuronal feedback loop between AVP and VIP neurons within the SCN is critical for the generation of the robust circadian.

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。本研究により中枢時計・視交叉上核が多くの時計ニューロンを統合して強固で安定した概日リズムを発振・発信する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により中枢時計を自在に制御する技術の開発にも繋がる。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • Research Products

    (38 results)

All 2025 2024 2023 2022 Other

All Int'l Joint Research (2 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (26 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results)

  • [Int'l Joint Research] University of California, San Diego(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University of Wurzburg(ドイツ)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Circadian rhythm mechanism in the suprachiasmatic nucleus and its relation to the olfactory system2024

    • Author(s)
      Tsuno Yusuke、Mieda Michihiro
    • Journal Title

      Frontiers in Neural Circuits

      Volume: 18 Pages: 1385908-1385908

    • DOI

      10.3389/fncir.2024.1385908

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo recording of the circadian calcium rhythm in Prokineticin 2 neurons of the suprachiasmatic nucleus2023

    • Author(s)
      Onodera Kaito、Tsuno Yusuke、Hiraoka Yuichi、Tanaka Kohichi、Maejima Takashi、Mieda Michihiro
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 16974-16974

    • DOI

      10.1038/s41598-023-44282-5

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Action sequence learning is impaired in genetically modified mice with the suppressed GABAergic transmission from the thalamic reticular nucleus to the thalamus2023

    • Author(s)
      Takako Ohno-Shosaku , Mitsugu Yoneda , Takashi Maejima , Mohan Wang , Yui Kikuchi , Kaito Onodera , Yuji Kanazawa , Chitoshi Takayama , Michihiro Mieda
    • Journal Title

      Neuroscience

      Volume: 532 Pages: 87-102

    • DOI

      10.1016/j.neuroscience.2023.09.019

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo recording of suprachiasmatic nucleus dynamics reveals a dominant role of arginine vasopressin neurons in circadian pacesetting2023

    • Author(s)
      Tsuno Yusuke、Peng Yubo、Horike Shin-ichi、Wang Mohan、Matsui Ayako、Yamagata Kanato、Sugiyama Mizuki、Nakamura Takahiro J.、Daikoku Takiko、Maejima Takashi、Mieda Michihiro
    • Journal Title

      PLOS Biology

      Volume: 21 Issue: 8 Pages: e3002281-e3002281

    • DOI

      10.1371/journal.pbio.3002281

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clock cells ticking in summer.2023

    • Author(s)
      Mieda M.
    • Journal Title

      Neuron

      Volume: 111 Issue: 14 Pages: 2119-2120

    • DOI

      10.1016/j.neuron.2023.06.022

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SIK3-HDAC4 in the suprachiasmatic nucleus regulates the timing of arousal at the dark onset and circadian period in mice2023

    • Author(s)
      Asano Fuyuki、Kim Staci J.、Fujiyama Tomoyuki、Miyoshi Chika、Hotta-Hirashima Noriko、Asama Nodoka、Iwasaki Kanako、Kakizaki Miyo、Mizuno Seiya、Mieda Michihiro、Sugiyama Fumihiro、Takahashi Satoru、Shi Shoi、Hirano Arisa、Funato Hiromasa、Yanagisawa Masashi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 120 Issue: 11 Pages: 1-11

    • DOI

      10.1073/pnas.2218209120

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Paraventricular hypothalamic vasopressin neurons induce self-grooming in mice2022

    • Author(s)
      Islam Md Tarikul、Maejima Takashi、Matsui Ayako、Mieda Michihiro
    • Journal Title

      Molecular Brain

      Volume: 15 Issue: 1 Pages: 47-47

    • DOI

      10.1186/s13041-022-00932-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vasopressin neurons in the paraventricular hypothalamus promote wakefulness via lateral hypothalamic orexin neurons2022

    • Author(s)
      Islam Md Tarikul、Rumpf Florian、Tsuno Yusuke、Kodani Shota、Sakurai Takeshi、Matsui Ayako、Maejima Takashi、Mieda Michihiro
    • Journal Title

      Current Biology

      Volume: 32 Issue: 18 Pages: 3871-3885

    • DOI

      10.1016/j.cub.2022.07.020

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Female fertility does not require Bmal1 in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S.2022

    • Author(s)
      Tonsfeldt KJ, Cui LJ, Lee J, Walbeek TJ, Brusman LE, Jin Y, Mieda M, Gorman MR, Mellon PL
    • Journal Title

      Front Endocrinol

      Volume: 13 Pages: 956169-956169

    • DOI

      10.3389/fendo.2022.956169

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] In vivo fiber photometry to reveal AVP neuronal function of the suprachiasmatic nucleus via cell-type specific labeling strategy2025

    • Author(s)
      Yusuke Tsuno, Takashi Maejima, Yubo Peng, Tomoyuki Fujiyama, Hiromasa Funato, Masashi Yanagisawa, Michihiro Mieda
    • Organizer
      APPW2025
    • Related Report
      2024 Annual Research Report
  • [Presentation] Prokineticin 2 neurons of the suprachiasmatic nucleus are essential for the circadian behavior rhythm2025

    • Author(s)
      Kaito Onodera, Yusuke Tsuno, Yuichi Hiraoka, Kohichi Tanaka, Takashi Maejima, Michihiro Mieda
    • Organizer
      APPW2025
    • Related Report
      2024 Annual Research Report
  • [Presentation] Arginine vasopressin-producing neurons in the suprachiasmatic nucleus require NALCN channel to retain resilience of circadian rhythm2025

    • Author(s)
      Takashi Maejima, Yusuke Tsuno, Tomoyuki Fujiyama, Yousuke Tsuneoka, Hiromasa Funato, Masashi Yanagisawa, Michihiro Mieda
    • Organizer
      APPW2025
    • Related Report
      2024 Annual Research Report
  • [Presentation] GIRK channel activation by the G-protein signal modulates the circadian rhythm of membrane properties of Prokinetin 2 neurons in the suprachiasmatic nucleus2025

    • Author(s)
      Jaehun Jung, Michihiro Mieda, Takashi Maejima
    • Organizer
      APPW2025
    • Related Report
      2024 Annual Research Report
  • [Presentation] Development of spike-and-wave discharges characteristic of absence seizures in genetically modified mice with the suppressed GABAergic transmission from the thalamic reticular nucleus to the thalamus2025

    • Author(s)
      Takako Ohno-Shosaku, Takashi Maejima, Yuji Kanazawa, Kenichiro Miyahara, Michihiro Mieda
    • Organizer
      APPW2025
    • Related Report
      2024 Annual Research Report
  • [Presentation] Characterization of EEG wave pattern in genetically modified mice with suppression of GABAergic transmission from the thalamic reticular nucleus to the thalamus2024

    • Author(s)
      Takako Ohno-Shosaku, Takashi Maejima, Yuji Kanazawa, Michihiro Mieda
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Circadian regulation of membrane properties of Prok2 neurons in the suprachiasmatic nucleus is mediated by G-protein signaling2024

    • Author(s)
      Jaehun Jung, Michihiro Mieda, Takashi Maejima
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] In vivo recording of the circadian calcium rhythm in Prokineticin 2 neurons of the suprachiasmatic nucleus2024

    • Author(s)
      Kaito Onodera, Yusuke Tsuno, Yuichi Hiraoka, Kohichi Tanaka, Takashi Maejima, Michihiro Mieda
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] VIP lengthens the intrinsically short circadian period of AVP neurons closer to 24 hours in the central clock of the SCN2024

    • Author(s)
      Mohan Wang, Yusuke Tsuno, Yubo Peng, Takashi Maejima, Michihiro Mieda
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] A GABAergic network mediates the regulation of VIP neurons by AVP neurons in the central circadian clock of the SCN2024

    • Author(s)
      Yubo Peng, Yusuke Tsuno, Mohan Wang, Takashi Maejima, Michihiro Mieda
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Arginine vasopressin-producing neurons in the suprachiasmatic nucleus require NALCN channel to retain resilience of circadian rhythm2024

    • Author(s)
      Takashi Maejima, Yusuke Tsuno, Tomoyuki Fujiyama, Yousuke Tsuneoka, Hiromasa Funato, Masashi Yanagisawa, Michihiro Mieda
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Neuronal network mechanisms underlying the central circadian clock of the SCN2024

    • Author(s)
      Michihiro Mieda
    • Organizer
      7th Asian Forum on Chronobiology in Sapporo
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neuronal network mechanisms underlying the central circadian clock of the SCN2024

    • Author(s)
      Michihiro Mieda
    • Organizer
      第31回日本時間生物学会学術大会
    • Related Report
      2024 Annual Research Report
    • Invited
  • [Presentation] VP neurons alter VIP neuronal Ca2+ activity and rhythm of locomotor activity in the suprachiasmatic nucleus2024

    • Author(s)
      Yusuke Tsuno、Yubo Peng、Takashi Maejim、Michihiro Mieda
    • Organizer
      第31回日本時間生物学会学術大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] 視交叉上核のバソプレッシン産生神経細胞に発現するNALCNチャネルは行動の概日リズムの回復力を保持するために必要である2024

    • Author(s)
      前島隆司, 津野祐輔, 藤山知之, 恒岡洋右, 船戸弘正, 柳沢正史, 三枝理博
    • Organizer
      第31回日本時間生物学会学術大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] VIP lengthens the intrinsically short circadian period of AVP neurons closer to 24 hours in the central clock of the SCN2024

    • Author(s)
      Mohan Wang, Yusuke Tsuno, Yubo Peng, Takashi Maejima, Michihiro Mieda
    • Organizer
      第31回日本時間生物学会学術大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] A GABAergic network mediates the regulation of VIP neurons by AVP neurons in the central circadian clock of the SCN2024

    • Author(s)
      Yubo Peng, Yusuke Tsuno, Mohan Wang, Takashi Maejima, Michihiro Mieda
    • Organizer
      第31回日本時間生物学会学術大会
    • Related Report
      2024 Annual Research Report
  • [Presentation] Genetic dissection of neural mechanisms underlying the central circadian clock2023

    • Author(s)
      Mieda M
    • Organizer
      日本睡眠学会/日本時間生物学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 神経細胞種特異的ノックアウトマウスを用いた視交叉上核概日リズムのin vivo 解析2023

    • Author(s)
      津野 祐輔、彭 雨波、堀家 慎一、王 墨涵、松井 綾子、山形 要人、杉山 瑞輝、中村 孝博、大黒 多希子、前島 隆司、三枝 理博
    • Organizer
      日本睡眠学会/日本時間生物学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Genetic dissection of neural mechanisms underlying the central circadian clock2023

    • Author(s)
      Mieda M
    • Organizer
      第100回日本生理学会学術大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Arginine vasopressin neurons of the suprachiasmatic nucleus act as the principal circadian pacesetter cells in vivo2023

    • Author(s)
      Tsuno Y, Peng Y, Horike S, Yamagata K, Sugiyama M, Nakamura TJ, Daikoku T, Maejima T, Mieda M
    • Organizer
      第100回日本生理学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] AVP neurons of the SCN control the ensemble period of the SCN network and locomotion period2022

    • Author(s)
      Tsuno Y, Peng Y, Horike S, Yamagata K, Sugiyama M, Nakamura TJ, Daikoku T, Maejima T, Mieda M
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2022 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44回日本神経科学大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Histological and behavioral characterization of Vip-tTA knock-in mice2022

    • Author(s)
      Peng Y, Tsuno Y, Matsui A, Hiraoka Y, Tanaka K, Horike SI, Daikoku T, Mieda M.
    • Organizer
      第29回日本時間生物学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 視交叉上核Prok2ニューロンの細胞内Ca2+リズムと概日行動2022

    • Author(s)
      小野寺海斗、津野祐輔、平岡優一、田中光一、三枝理博
    • Organizer
      第29回日本時間生物学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Critical roles of AVP neurons in the central circadian clock of the SCN network2022

    • Author(s)
      Mieda M
    • Organizer
      Sapporo Symposium on Biological Rhythm
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2022-04-19   Modified: 2026-01-16  

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