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Understanding the neural mechanisms underlying the central circadian pacemaker by neuron type-specific genetic manipulations

Research Project

Project/Area Number 16H05120
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionKanazawa University

Principal Investigator

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

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2016: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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 / 視交叉上核 / バソプレシン / GABA / 組換えAAVベクター / ファイバーフォトメトリー / 概日リズム / マウス / in vivo / 血管作動性腸管ペプチド / 時計遺伝子 / トランスジェニックマウス
Outline of Final Research Achievements

In this study, we aimed to understand the neural mechanisms underlying the generation of robust and stable circadian rhythms by the central circadian pacemaker of the suprachiasmatic nucleus (SCN), utilizing genetically-modified mice which we have developed.
We found that vasopressin-producing neurons, one of major neuron types in the SCN, play a critical role in the generation of circadian rhythms and the determination of circadian period by the SCN neural network. In addition, we analyzed the electrophysiological characteristics of vasopressin neurons and other types of neurons in the SCN. Before this study, vasopressin neurons had been considered to be dispensable for the generation per se of circadian rhythms by the SCN network. Thus, our findings reversed the conventional views about the role of vasopressin neurons in the central circadian pacemaker.

Academic Significance and Societal Importance of the Research Achievements

我々の行動や生理機能の殆どが概日リズムにより調節されるため、その変調により不眠、肥満や気分障害等、様々な健康障害・疾患リスクが増大する。現代社会では、時差や夜間勤務、生活習慣の乱れにより、概日リズムの変調は誰にでも起こりうる。本研究の成果により、SCN神経ネットワークを構成する各ニューロンの役割や、中枢体内時計の神経メカニズムが明らかになれば、概日リズム変調による様々な疾患・健康障害に対し、薬剤投与による概日リズムの調整など、より効果的に対処できる技術の開発を、大いに期待できる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (35 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (5 results) Journal Article (14 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 14 results,  Open Access: 11 results,  Acknowledgement Compliant: 1 results) Presentation (15 results) (of which Int'l Joint Research: 5 results,  Invited: 9 results) Remarks (1 results)

  • [Int'l Joint Research] Tufts University(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Medical Research Council(英国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ワシントン大学(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Washington University(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University College London(英国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Sexually Dimorphic Vasopressin Cells Modulate Social Investigation and Communication in Sex-Specific Ways.2019

    • Author(s)
      Rigney N, Whylings J, Mieda M, de Vries G, Petrulis A
    • Journal Title

      eNeuro

      Volume: 6 Issue: 1 Pages: ENEURO.0415-18.2019

    • DOI

      10.1523/eneuro.0415-18.2019

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glutamatergic neurons in the medial prefrontal cortex mediate the formation and retrieval of cocaine-associated memories in mice2019

    • Author(s)
      Zhang Tong、Yanagida Junko、Kamii Hironori、Wada Shintaro、Domoto Masaki、Sasase Hitoki、Deyama Satoshi、Takarada Takeshi、Hinoi Eiichi、Sakimura Kenji、Yamanaka Akihiro、Maejima Takashi、Mieda Michihiro、Sakurai Takeshi、Nishitani Naoya、Nagayasu Kazuki、Kaneko Shuji、Minami Masabumi、Kaneda Katsuyuki
    • Journal Title

      Addiction Biology

      Volume: 印刷中 Issue: 1 Pages: 1-11

    • DOI

      10.1111/adb.12723

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Network Mechanism of the Central Circadian Pacemaker of the SCN: Do AVP Neurons Play a More Critical Role Than Expected?2019

    • Author(s)
      Mieda M.
    • Journal Title

      Front Neurosci

      Volume: 13 Pages: 139-139

    • DOI

      10.3389/fnins.2019.00139

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Monoamines Inhibit GABAergic Neurons in Ventrolateral Preoptic Area That Make Direct Synaptic Connections to Hypothalamic Arousal Neurons2018

    • Author(s)
      Saito Yuki C.、Maejima Takashi、Nishitani Mitsuhiro、Hasegawa Emi、Yanagawa Yuchio、Mieda Michihiro、Sakurai Takeshi
    • Journal Title

      The Journal of Neuroscience

      Volume: 38 Issue: 28 Pages: 6366-6378

    • DOI

      10.1523/jneurosci.2835-17.2018

    • NAID

      120007133906

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Time Restriction of Food Intake During the Circadian Cycle Is a Possible Regulator of Reproductive Function in Postadolescent Female Rats.2018

    • Author(s)
      Fujiwara T, Nakata R, Ono M, Mieda M, Ando H, Daikoku T, Fujiwara H.
    • Journal Title

      Curr Dev Nutr

      Volume: 3 Issue: 4 Pages: 1-7

    • DOI

      10.1093/cdn/nzy093

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Astrocytes Regulate Daily Rhythms in the Suprachiasmatic Nucleus and Behavior.2017

    • Author(s)
      Tso CF, Simon T, Greenlaw AC, Puri T, Mieda M, Herzog ED
    • Journal Title

      Curr Biol.

      Volume: 27 Issue: 7 Pages: 1055-1061

    • DOI

      10.1016/j.cub.2017.02.037

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serotonin neurons of the dorsal raphe mediate the anti-cataplectic action of orexin neurons by reducing the amygdala activity2017

    • Author(s)
      Hasegawa, E., Maejima, T., Yoshida, T., Masseck O.A., Herlitze, S., Yoshioka, M., Sakurai, T., Mieda, M.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 114 Issue: 17

    • DOI

      10.1073/pnas.1614552114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The roles of orexins in sleep/wake regulation2017

    • Author(s)
      Mieda Michihiro
    • Journal Title

      Neurosci Res

      Volume: 118 Pages: 56-65

    • DOI

      10.1016/j.neures.2017.03.015

    • NAID

      120006336007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disruption of Bmal1 Impairs Blood?Brain Barrier Integrity via Pericyte Dysfunction2017

    • Author(s)
      Nakazato Ryota、Kawabe Kenji、Yamada Daisuke、Ikeno Shinsuke、Mieda Michihiro、Shimba Shigeki、Hinoi Eiichi、Yoneda Yukio、Takarada Takeshi
    • Journal Title

      The Journal of Neuroscience

      Volume: 37 Issue: 42 Pages: 10052-10062

    • DOI

      10.1523/jneurosci.3639-16.2017

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The intrinsic microglial clock system regulates interleukin-6 expression.2017

    • Author(s)
      Ryota Nakazato, Shogo Hotta, Daisuke Yamada, Miki Kou, Saki Nakamura, Yoshifumi Takahata, Hajime Tei, Rika Numano, Akiko Hida, Shigeki Shimba, Michihiro Mieda, Eiichi Hinoi, Yukio Yoneda and Takeshi Takarada
    • Journal Title

      Glia

      Volume: 65 Issue: 1 Pages: 198-208

    • DOI

      10.1002/glia.23087

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Fine-Tuning Circadian Rhythms: The Importance of Bmal1 Expression in the Ventral Forebrain.2017

    • Author(s)
      Mieda M, Hasegawa E, Kessaris N, Sakurai T
    • Journal Title

      Front Neurosci.

      Volume: 11 Pages: 55-55

    • DOI

      10.3389/fnins.2017.00055

    • NAID

      120006027787

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Synchronous circadian voltage rhythms with asynchronous calcium rhythms in the suprachiasmatic nucleus.2017

    • Author(s)
      Enoki R, Oda Y, Mieda M, Ono D, Honma S, Honma KI
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 114 Issue: 12 Pages: 2476-2485

    • DOI

      10.1073/pnas.1616815114

    • NAID

      120006346107

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Manipulating the Cellular Circadian Period of Arginine Vasopressin Neurons Alters the Behavioral Circadian Period.2016

    • Author(s)
      Mieda M, Okamoto H, Sakurai T.
    • Journal Title

      Curr Biol.

      Volume: S0960-9822(16) Issue: 18 Pages: 30773-4

    • DOI

      10.1016/j.cub.2016.07.022

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] QRFP-deficient mice are hypophagic, lean, hypoactive and exhibit increased anxiety-like behavior2016

    • Author(s)
      Okamoto K, Yamasaki M, Takao K, Soya S, Iwasaki M, Sasaki K, Magoori K, Sakakibara I, Miyakawa T, Mieda M, Watanabe M, Sakai J, Yanagisawa M, Sakurai T
    • Journal Title

      PLoS ONE

      Volume: 11 Issue: 11 Pages: e0164716-e0164716

    • DOI

      10.1371/journal.pone.0164716

    • NAID

      120007129233

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 哺乳類中枢概日時計の神経メカニズム2019

    • Author(s)
      三枝理博
    • Organizer
      明治大学現象数理学共同研究集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Analysis of the central circadian clock in AVP neuron-specific VGAT deficient mice2019

    • Author(s)
      前島隆司 長谷川恵美 津野祐輔 三枝理博
    • Organizer
      第9回アジア・オセアニア生理学会連合(FAOPS)2019年大会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 中枢概日時計におけるバソプレシンニューロンの機能2018

    • Author(s)
      三枝理博
    • Organizer
      第43回日本睡眠学会定期学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Genetic dissection of neural mechanisms underlying the central circadian pacemaker2018

    • Author(s)
      三枝理博
    • Organizer
      Sapporo Symposium on Biological Rhythm in 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neural mechanisms underlying the central circadian pacemaker of the SCN2018

    • Author(s)
      三枝理博
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] AVP神経特異的小胞GABAトランスポーター遺伝子欠損マウスにおける中枢概日時計の解析2018

    • Author(s)
      前島隆司、長谷川恵美、津野祐輔、三枝理博
    • Organizer
      第25回日本時間生物学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 視交叉上核の中枢概日時計におけるAVPニューロンの役割2018

    • Author(s)
      三枝理博
    • Organizer
      日本生理学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] バソプレシン産生ニューロンは視交叉上核のペースメーカー機能に重要な役割を果たす2017

    • Author(s)
      三枝理博
    • Organizer
      日本生理学会
    • Place of Presentation
      アクトシティ浜松 (静岡県浜松市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Genetic manipulation of AVP neurons to uncover their roles in the circadian pacemaking of the SCN2017

    • Author(s)
      Mieda M, Ono D, Hasegawa E, Okamoto H, Honma S, Honma K, akurai T.
    • Organizer
      Gordon Research Conference-Chronobiology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 中枢概日時計の神経メカニズムの解析2017

    • Author(s)
      三枝理博
    • Organizer
      中部日本生理学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] AVPニューロンの細胞時計の周期に応じて概日行動リズムの周期も変化する2017

    • Author(s)
      三枝理博、岡本仁、櫻井武
    • Organizer
      日本時間生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] オレキシンによる睡眠・覚醒調節の神経メカニズム2017

    • Author(s)
      三枝理博
    • Organizer
      生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] AVP neurons play a critical role in the circadian pacemaking of the SCN.2016

    • Author(s)
      Mieda M
    • Organizer
      Sapporo Symposium on Biological Rhythm
    • Place of Presentation
      北海道大学(北海道札幌市)
    • Year and Date
      2016-11-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] AVPニューロンの細胞時計の周期に応じて概日行動リズムの周期も変化する2016

    • Author(s)
      三枝理博、岡本仁、櫻井武
    • Organizer
      日本神経科学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] Manipulating the cellular circadian period of AVP neurons alters the behavioral circadian period.2016

    • Author(s)
      Mieda M, Okamoto H, Sakurai T
    • Organizer
      Society for Research on Biological Rhythms (SRBR)
    • Place of Presentation
      The Innisbrook Golf Resort (Palm Harbor, Florida, USA)
    • Year and Date
      2016-05-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 体内時計が刻む1日の長さを決める細胞を発見!

    • URL

      http://www.kanazawa-u.ac.jp/rd/40314

    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2022-05-20  

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