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Understanding of neuronal circuits that are related circadian clock regulated sleep/wakefulness

Research Project

Project/Area Number 18H02477
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
Research InstitutionNagoya University

Principal Investigator

Ono Daisuke  名古屋大学, 環境医学研究所, 講師 (30634224)

Co-Investigator(Kenkyū-buntansha) 徳田 功  立命館大学, 理工学部, 教授 (00261389)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords概日リズム / 睡眠 / 神経回路 / 光遺伝学 / 光イメージング / 光操作 / 光計測 / 概日時計
Outline of Final Research Achievements

To understand neuronal circuits that are related with the circadian clock regulated sleep/wakefulness, we performed anterograde tracing, optogenetics, pharmacogenetics, in vivo fiber photometry, neuronal ablation, bioluminescence imaging. Finally, we identified one specific neuronal pathway in the hypothalamus that regulates the circadian clock regulated wakefulness. GABAergic neurons in the central circadian clock, suprachiasmatic nucleus (SCN), innervate corticosterone releasing factor (CRF) neurons in the paraventricular nucleus (PVN) in the hypothalamus, and these neurons increase time in wakefulness via orexin neurons in the lateral hypothalamus.

Academic Significance and Societal Importance of the Research Achievements

これまで視床下部に位置する視交叉上核は、概日リズムに重要な神経細胞として知られていたが、そこからどのような神経経路を介して、睡眠・覚醒のタイミングが調節されているかは、これまでほとんど理解が進んでいなかった。本研究では、概日時計が調節する神経回路の一端を世界で初めて明らかにした結果である。本研究結果は、概日時計機能の破綻による睡眠障害や、その他の生理機能の破綻を治療可能なあらたな治療法開発に大きな影響を与えるものである。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (45 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (6 results) Journal Article (12 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 12 results,  Open Access: 7 results) Presentation (19 results) (of which Int'l Joint Research: 7 results,  Invited: 5 results) Book (1 results) Remarks (7 results)

  • [Int'l Joint Research] Center for Neuroscience/Biosciences Division, SRI International(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] SRI International(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Groningen(オランダ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Universita¨tsmedizin Berlin(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Vanderbilt University(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Taipei Medical University(その他の国・地域 (台湾))

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Roles of Neuropeptides, VIP and AVP, in the Mammalian Central Circadian Clock2021

    • Author(s)
      Ono Daisuke、Honma Ken-ichi、Honma Sato
    • Journal Title

      Frontiers in Neuroscience

      Volume: 15 Pages: 650154-650154

    • DOI

      10.3389/fnins.2021.650154

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The mammalian circadian pacemaker regulates wakefulness via CRF neurons in the paraventricular nucleus of the hypothalamus.2020

    • Author(s)
      *Ono D, Mukai Y, Hung CJ, Chowdhury S, Sugiyama T, *Yamanaka A.
    • Journal Title

      Sci Adv

      Volume: 6(45) Issue: 45 Pages: 0384-0384

    • DOI

      10.1126/sciadv.abd0384

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GABAergic mechanisms in the suprachiasmatic nucleus that influence circadian rhythm2020

    • Author(s)
      Ono Daisuke、Honma Ken‐ichi、Honma Sato
    • Journal Title

      Journal of Neurochemistry

      Volume: 157 Issue: 1 Pages: 31-41

    • DOI

      10.1111/jnc.15012

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual Orexin and MCH neuron-ablated mice display severe sleep attacks and cataplexy.2020

    • Author(s)
      Hung, J.C., Ono, D., Kilduff, S.T., and Yamanaka, A.
    • Journal Title

      eLife

      Volume: なし Pages: 9-9

    • DOI

      10.7554/elife.54275

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Controlling the Circadian Clock with High Temporal Resolution through Photodosing2019

    • Author(s)
      Kolarski Dusan、Sugiyama Akiko、Breton Ghislain、Rakers Christin、Ono Daisuke、Schulte Albert、Tama Florence、Itami Kenichiro、Szymanski Wiktor、Hirota Tsuyoshi、Feringa Ben L.
    • Journal Title

      Journal of the American Chemical Society

      Volume: 141 Issue: 40 Pages: 15784-15791

    • DOI

      10.1021/jacs.9b05445

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] REM sleep?active MCH neurons are involved in forgetting hippocampus-dependent memories2019

    • Author(s)
      Izawa Shuntaro、Chowdhury Srikanta、Miyazaki Toh、Mukai Yasutaka、Ono Daisuke、Inoue Ryo、Ohmura Yu、Mizoguchi Hiroyuki、Kimura Kazuhiro、Yoshioka Mitsuhiro、Terao Akira、Kilduff Thomas S.、Yamanaka Akihiro
    • Journal Title

      Science

      Volume: 365 Issue: 6459 Pages: 1308-1313

    • DOI

      10.1126/science.aax9238

    • NAID

      120006777541

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GABA in the suprachiasmatic nucleus refines circadian output rhythms in mice.2019

    • Author(s)
      Ono D, Honma KI, Yanagawa Y, Yamanaka A, Honma S
    • Journal Title

      Commun Biol.

      Volume: 2 Issue: 1 Pages: 232-232

    • DOI

      10.1038/s42003-019-0483-6

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GABA neurons in the ventral tegmental area regulate non-rapid eye movement sleep in mice2019

    • Author(s)
      Chowdhury Srikanta、Matsubara Takanori、Miyazaki Toh、Ono Daisuke、Fukatsu Noriaki、Abe Manabu、Sakimura Kenji、Sudo Yuki、Yamanaka Akihiro
    • Journal Title

      eLife

      Volume: 8

    • DOI

      10.7554/elife.44928

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Weak coupling between intracellular feedback loops explains dissociation of clock gene dynamics2019

    • Author(s)
      Schmal Christoph、Ono Daisuke、Myung Jihwan、Pett J. Patrick、Honma Sato、Honma Ken-Ichi、Herzel Hanspeter、Tokuda Isao T.
    • Journal Title

      PLOS Computational Biology

      Volume: 15 Issue: 9 Pages: e1007330-e1007330

    • DOI

      10.1371/journal.pcbi.1007330

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Chemical Control of Mammalian Circadian Behavior through Dual Inhibition of Casein Kinase Iα and δ2019

    • Author(s)
      Lee Jae Wook、Hirota Tsuyoshi、Ono Daisuke、Honma Sato、Honma Ken-ichi、Park Keunwan、Kay Steve A.
    • Journal Title

      Journal of Medicinal Chemistry

      Volume: 62 Issue: 4 Pages: 1989-1998

    • DOI

      10.1021/acs.jmedchem.8b01541

    • NAID

      120006645104

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Role of GABA in the regulation of the central circadian clock of the suprachiasmatic nucleus2018

    • Author(s)
      Ono, Daisuke, Honma, Ken-ichi, Yanagawa, Yuchio, Yamanaka, Akihiro, and Honma, Sato
    • Journal Title

      The journal of physiological sciences

      Volume: 68 Pages: 333-343

    • NAID

      120006517655

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coherency of circadian rhythms in the SCN is governed by the interplay of two coupling factors2018

    • Author(s)
      Tokuda Isao T.、Ono Daisuke、Honma Sato、Honma Ken-Ichi、Herzel Hanspeter
    • Journal Title

      PLOS Computational Biology

      Volume: 14 Issue: 12 Pages: 1006607-1006607

    • DOI

      10.1371/journal.pcbi.1006607

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Postnatal Development of the Cellular Networks in the Suprachiasmatic Nucleus2020

    • Author(s)
      Daisuke Ono
    • Organizer
      Society for research on biological rhythms 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 概日時計と睡眠・覚醒を繋ぐ神経回路2020

    • Author(s)
      小野大輔
    • Organizer
      シナプス研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] The suprachiasmatic nucleus regulates wakefulness via CRF neurons in the paraventricular nucleus of the hypothalamus2020

    • Author(s)
      小野大輔
    • Organizer
      日本時間生物学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The suprachiasmatic nucleus regulates wakefulness via CRF neurons in the hypothalamus2020

    • Author(s)
      Ono, D., Hung, C. J, Chowdury, S., Wang, G., and Yamanaka A.
    • Organizer
      日本生理学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] GABA in the suprachiasmatic nucleus refines circadian behavioral rhythms.2019

    • Author(s)
      Ono, D., Honma, K., Yanagawa, Y., Yamanaka, A., and Honma, K.
    • Organizer
      V World Congress of Chronobiology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The suprachiasmatic nucleus regulates wakefulness via CRF neurons in the hypothalamus.2019

    • Author(s)
      Ono, D., Hung, C. J, Chowdury, S., Wang, G., and Yamanaka A.
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 視交叉上核が睡眠覚醒を調節する神経回路の探索2019

    • Author(s)
      小野大輔,Hung Chi Jung,Srikanta Chowdhury,Wang Guanyi,山中章弘
    • Organizer
      第26回日本時間生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Optical recording and manipulation of cAMP in the central circadian clock neurons2019

    • Author(s)
      Daisuke Ono, Hung Chi Jung, Takashi Sugiyama, Akihiro Yamanaka.
    • Organizer
      第11回光操作研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] GABA in the suprachiasmatic nucleus refines circadian behavioral rhythms2019

    • Author(s)
      Ono, D., Honma, K., Yanagawa, Y., Yamanaka, A., and Honma, K.
    • Organizer
      AOPS2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Application of bioluminescence proteins for measurement of gene expression in vivo and ex vivo2018

    • Author(s)
      Ono, D., Honma, S., and Honma, K.
    • Organizer
      IBRO APRC School 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Postnatal development of cellular networks in the mammalian central circadian clock2018

    • Author(s)
      Ono, D., Honma, S., and Honma, K.
    • Organizer
      IBRO APRC School 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] GABA refines circadian output rhythms in the mouse suprachiasmatic nucleus2018

    • Author(s)
      Ono, D., Honma, K., Yanagawa, Y., and Honma, S.
    • Organizer
      International Symposium on Biological Rhythms
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel function of GABA in the mouse suprachiasmatic nucleus: refinement of circadian output rhythms2018

    • Author(s)
      Ono, D., Honma, K., Yanagawa, Y., and Honma, S.
    • Organizer
      Society for research on biological rhythms 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 概日時計が調節する睡眠覚醒の神経回路2018

    • Author(s)
      小野大輔
    • Organizer
      第3回ルミノジェネティクス研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 光ファイバーを用いた自由行動下マウス脳内の時計遺伝子発現計測2018

    • Author(s)
      小野大輔,本間研一,本間さと
    • Organizer
      第43回日本睡眠学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 概日時計が調節する睡眠覚醒の神経回路2018

    • Author(s)
      小野大輔
    • Organizer
      第3回ルミノジェネティクス研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 光遺伝学と併用可能な光イメージングツールの開発と応用2018

    • Author(s)
      小野大輔,Hung Chi Jung,Srikanta Chowdhury,山中章弘
    • Organizer
      第三回名古屋リズム研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 室傍核コルチコトロピン放出因子神経は覚醒を誘導する2018

    • Author(s)
      小野大輔,Hung Chi Jung,Srikanta Chowdhury,山中章弘
    • Organizer
      第25回日本時間生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] GABA refines circadian output rhythms in the mouse suprachiasmatic nucleus2018

    • Author(s)
      小野大輔,本間研一,柳川右千夫,本間さと
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Book] 基礎医学からみた概日リズムと睡眠の科学2019

    • Author(s)
      小野大輔
    • Total Pages
      115
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2018 Annual Research Report
  • [Remarks] 研究室HP

    • URL

      http://www.riem.nagoya-u.ac.jp/4/neuroscience2/nr/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 独自HP

    • URL

      https://daiono14.wixsite.com/circadianrhythm

    • Related Report
      2020 Annual Research Report
  • [Remarks] 睡眠発作を起こし、脱力発作を悪化させる仕組みを解明

    • URL

      http://www.riem.nagoya-u.ac.jp/images/Jeffrey_pdf.pdf

    • Related Report
      2019 Annual Research Report
  • [Remarks] 浅い眠りで記憶が消去される仕組みを解明

    • URL

      https://www.med.nagoya-u.ac.jp/medical_J/research/pdf/Sci_190920.pdf

    • Related Report
      2019 Annual Research Report
  • [Remarks] 脳内の概日時計における抑制性神経の機能を発見

    • URL

      https://www.med.nagoya-u.ac.jp/medical_J/research/pdf/Com_Bio_20190621.pdf

    • Related Report
      2019 Annual Research Report
  • [Remarks] ノンレム睡眠を調節する新しい神経細胞の発見

    • URL

      http://www.riem.nagoya-u.ac.jp/images/RIEM_VTA-GABA.pdf

    • Related Report
      2019 Annual Research Report
  • [Remarks] 光を用いた概日リズムの精密な調節

    • URL

      http://www.itbm.nagoya-u.ac.jp/ja/research/ITbM-Hirota-20191002_final-modifyv2.pdf

    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2022-08-19  

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