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Hierarchical self-organization of circadian system: synchronization of cellular oscillators and pacemaker coupling

Research Project

Project/Area Number 15H04679
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology(including physical medicine and nutritional physiology)
Research InstitutionHokkaido University

Principal Investigator

HONMA Sato  北海道大学, 脳科学研究教育センター, 招へい教員 (20142713)

Co-Investigator(Kenkyū-buntansha) 榎木 亮介  北海道大学, 電子科学研究所, 准教授 (00528341)
小野 大輔  名古屋大学, 環境医学研究所, 助教 (30634224)
Co-Investigator(Renkei-kenkyūsha) TOKUDA Isao  立命館大学, 理工学部, 教授 (00261389)
Research Collaborator MIEDA Michihiro  
OHMIYA Yoshihiro  
NAKAJIMA Yoshihiro  
KURODA Shigeru  
TAKAGI Seiji  
YOSHIKAWA Tomoko  
ODA Yoshiaki  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords生体リズム / 時計遺伝子 / 視交叉上核 / イメージング / 結合振動子 / 概日リズム
Outline of Final Research Achievements

We aimed to clarify the self-organizing mechanisms for the hierarchical multi-oscillator structure of the mammalian circadian clock in the suprachiasmatic nucleus (SCN) using knockout mice for clock genes and neuropeptides functions, luciferase reporter mice for continuous monitoring clock gene expression, and fluorescence sensors for monitoring intracellular calcium and membrane potentials. We demonstrated that both VIP and vasopressin act as synchronizers for cellular rhythms. We also found that their roles change depending on postnatal development, in which clock gene Cry is involved. We also found that GABA in the SCN acts not in cellular rhythm generation but in coherent neural rhythm output from the SCN to make the central circadian clock free of bursts. We further found that Per1 rhythms in the discrete areas in the SCN are involved in transferring photoperiodic signals to behavior rhythm output by changing the phase relations.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (42 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (17 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 16 results,  Open Access: 12 results,  Acknowledgement Compliant: 4 results) Presentation (17 results) (of which Int'l Joint Research: 12 results,  Invited: 17 results) Book (4 results) Funded Workshop (1 results)

  • [Int'l Joint Research] コロンビア大学/ダートマス大学(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] グローニンゲン大学(オランダ)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] フンボルト大学/シャリテーベルリン医科大学(ドイツ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] The mammalian circadian system: a hierarchical multi-oscillator structure for generating circadian rhythm2018

    • Author(s)
      Honma Sato
    • Journal Title

      J.Physiol.Sci.

      Volume: 68 Issue: 3 Pages: 207-219

    • DOI

      10.1007/s12576-018-0597-5

    • NAID

      40021532533

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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、Honma Sato
    • Journal Title

      J.Physiol.Sci.

      Volume: 68 Issue: 4 Pages: 333-343

    • DOI

      10.1007/s12576-018-0604-x

    • NAID

      120006517655

    • Related Report
      2017 Annual Research Report
    • Open Access
  • [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
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dissociation of Per1 and Bmal1 circadian rhythms in the suprachiasmatic nucleus in parallel with behavioral outputs.2017

    • Author(s)
      Ono, D., Honma, S., Nakajima, Y., Kuroda, S., Enoki, R., and Honma, K.
    • Journal Title

      Proc. Natl. Acad. Sci. U S A.

      Volume: 114 Issue: 18 Pages: 3699-3708

    • DOI

      10.1073/pnas.1613374114

    • NAID

      120006331822

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Localization of photoperiod responsive circadian oscillators in the mouse suprachiasmatic nucleus2017

    • Author(s)
      Yoshikawa Tomoko、Inagaki Natsuko F.、Takagi Seiji、Kuroda Shigeru、Yamasaki Miwako、Watanabe Masahiko、Honma Sato、Honma Ken-ichi
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 820-820

    • DOI

      10.1038/s41598-017-08186-5

    • NAID

      120006360085

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo imaging of clock gene expression in multiple tissues of freely moving mice.2016

    • Author(s)
      Hamada T, Sutherland K, Ishikawa M, Miyamoto N, Honma S, Shirato H, Honma K.
    • Journal Title

      Nat.Commn.

      Volume: 7 Issue: 1 Pages: 11705-11705

    • DOI

      10.1038/ncomms11705

    • NAID

      120005820742

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deconstructing Circadian Rhythmicity with Models and Manipulations.2016

    • Author(s)
      Pauls SD, Honma KI, Honma S, Silver R.
    • Journal Title

      Trends Neurosci.

      Volume: 39 Issue: 6 Pages: 405-419

    • DOI

      10.1016/j.tins.2016.03.006

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lithium lengthens circadian period of cultured brain slices in area specific manner.2016

    • Author(s)
      Yoshikawa T, Honma S
    • Journal Title

      Behav Brain Res

      Volume: 314 Pages: 30-37

    • DOI

      10.1016/j.bbr.2016.07.045

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN2016

    • Author(s)
      Ono, D., Honma, S., and Honma, K.
    • Journal Title

      Science Advances

      Volume: 2 Issue: 9

    • DOI

      10.1126/sciadv.1600960

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mistimed wheel-running interferes with re-entrainment of circadian Per1 rhythms to shifted light-dark cycles in the mouse skeletal muscle and lung2015

    • Author(s)
      Yamanaka Y, Honma S and Honma K.
    • Journal Title

      Genes Cells

      Volume: 21 Issue: 3 Pages: 264-274

    • DOI

      10.1111/gtc.12336

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cellular Clocks in AVP Neurons of the SCN Are Critical for Interneuronal Coupling Regulating Circadian Behavior Rhythm.2015

    • Author(s)
      Mieda M, Ono D, Hasegawa E, Okamoto H, Honma K, Honma S, Sakurai T.
    • Journal Title

      Neuron

      Volume: 85 Issue: 5 Pages: 1103-1116

    • DOI

      10.1016/j.neuron.2015.02.005

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Circadian and ultradian rhythms of clock gene expression in the suprachiasmatic nucleus of freely moving mice2015

    • Author(s)
      Ono D, Honma K and Honma S.
    • Journal Title

      Sci. Rep.

      Volume: 5 Issue: 1 Pages: 12310-12310

    • DOI

      10.1038/srep12310

    • NAID

      120005625313

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spatiotemporal profiles of arginine vasopressin transcription in cultured suprachiasmatic nucleus.2015

    • Author(s)
      Yoshikawa, T.;Nakajima, Y.;Yamada, Y.;Enoki, R.;Watanabe, K.;Yamazaki, M.;Sakimura, K.;Honma, S.;Honma, K.
    • Journal Title

      Eur J NEUROSC

      Volume: 42 Issue: 9 Pages: 2411-2423

    • DOI

      10.1111/ejn.13061

    • NAID

      120005853065

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucocorticoids reset the nasal circadian clock in mice2015

    • Author(s)
      Honma A, Yamada Y, Nakamaru Y, Fukuda S, Honma K. and Honma S.
    • Journal Title

      Endocrinology

      Volume: 156 Issue: 11 Pages: 4302-4311

    • DOI

      10.1210/en.2015-1490

    • NAID

      120005712481

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Circadian PER2::LUC rhythms in the olfactory bulb of freely moving mice depend on the SCN but not on behavior rhythms2015

    • Author(s)
      Ono D, Honma S and Honma K.
    • Journal Title

      Eur. J. Neurosci.

      Volume: 42 Issue: 12 Pages: 3128-3137

    • DOI

      10.1111/ejn.13111

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Morning and evening physical exercise differentially regulate the autonomic nervous system during nocturnal sleep in human2015

    • Author(s)
      Yamanaka Y, Hashimoto S, Takasu NN, Tanahashi Y, Nishide S, Honma S and Honma K.
    • Journal Title

      Am J Physiol Reg Integ Comp Physiol

      Volume: R309 Issue: 9 Pages: R1112-R1121

    • DOI

      10.1152/ajpregu.00127.2015

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coupling controls synchrony of clock cells in development and knockouts2015

    • Author(s)
      Tokuda, I., Ono, D., Ananthasubramaniam, B., Honma, S., Honma, K., and Herzel, H.
    • Journal Title

      Biophysical Journal

      Volume: 109 Issue: 10 Pages: 2159-2170

    • DOI

      10.1016/j.bpj.2015.09.024

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] In vivo monitoring of circadian rhythms revealed tissue specific regulation of peripheral clocks by the master circadian pacemaker2017

    • Author(s)
      Honma S
    • Organizer
      2nd Asian Forum on Chronobiology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] In vivo monitoring of clock gene expression from freely moving mice,2017

    • Author(s)
      Honma S
    • Organizer
      Special Lectures in Chronobiology, University of Hyderabad
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Seep in health and bipolar disorders.2017

    • Author(s)
      Honma S
    • Organizer
      25th ISSR 2017 Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Oscillators in the suprachiasmatic nucleus regulating seasonality in sleep-wake rhythm.2017

    • Author(s)
      Honma S.
    • Organizer
      World Sleep 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Simultaneous measurement of circadian rhythms of multiple functions: Dissociation of Per1 and Bmal1 circadian rhythms in the suprachiasmatic nucleus.2017

    • Author(s)
      Ono D
    • Organizer
      15th European Biological Rhythm Society Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Unveiling functions of the central circadian clock by imaging “clock time”2016

    • Author(s)
      本間さと
    • Organizer
      第93回日本生理学会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌市)
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] VIP and AVP signaling regulate circadian cellular networks in the suprachiasmatic nucleus during postnatal development.2016

    • Author(s)
      小野大輔、本間さと、本間研一
    • Organizer
      第93回日本生理学会大会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌市)
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Suprachiasmatic Nucleus: A master circadian pacemaker of mammals.2016

    • Author(s)
      Honma S
    • Organizer
      3rd International Chrono Summer School
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Oscillator networks in the suprachiasmatic nucleus.2016

    • Author(s)
      Honma S
    • Organizer
      29th Chronobiologia International Congress,
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Circadian Bmal1 and Per2 rhythms driven by different oscillators in the suprachiasmatic nucleus.2016

    • Author(s)
      Ono D
    • Organizer
      Sapporo Synmposium on Biological Rhythms 2016
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Asynchronous Ca2+ rhythms produce synchronous voltage rhythms in the suprachiasmatic nucleus2016

    • Author(s)
      Enoki R
    • Organizer
      Sapporo Synmposium on Biological Rhythms 2016
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 双極性障害における概日リズム障害:時計遺伝子レポーターによる解析2016

    • Author(s)
      本間さと
    • Organizer
      第12 回日本うつ病学会総会・第15 回日本認知療法学会
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 双極性障害と概日リズム2016

    • Author(s)
      本間さと
    • Organizer
      第35回リチウム研究会
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Bioluminescence imaging analyses revealed localization of evening and morning circadian oscillators in mouse suprachiasmatic nucleus2015

    • Author(s)
      Yoshikawa T, Kuroda S, Takagi S, Ueda T, Honma S and Honma K
    • Organizer
      Asian Forum on Chronobiology 2015
    • Place of Presentation
      Hokkaido Univ Conference Center,(北海道・札幌市)
    • Year and Date
      2015-09-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] VIP and AVP regulate circadian cellular networks in the suprachiasmatic nucleus of Cryptochrome deficient mice during postnatal development2015

    • Author(s)
      Ono D, Honma S and Honma K
    • Organizer
      Asian Forum on Chronobiology 2015
    • Place of Presentation
      Hokkaido Univ Conference Center, (北海道・札幌市)
    • Year and Date
      2015-09-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Multicolor imaging of circadian rhythms in neuronal network of the suprachiasmatic nucleus,2015

    • Author(s)
      Enoki R, Ono S, Mieda M. Honma S and Honma K.
    • Organizer
      14th Europen Biological Rhyty Society Meeting
    • Place of Presentation
      Manchester (UK)
    • Year and Date
      2015-08-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Circadian cell networks in the suprachiasmatic nucleus during the postnatal development.2015

    • Author(s)
      Ono D, Honma S, and Honma K.
    • Organizer
      第38回日本神経科学学会大会
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Book] サーカディアンリズムと睡眠2018

    • Author(s)
      本間さと
    • Publisher
      新興医学出版社
    • Related Report
      2017 Annual Research Report
  • [Book] 睡眠学第二版2018

    • Author(s)
      本間さと
    • Publisher
      朝倉書店
    • Related Report
      2017 Annual Research Report
  • [Book] Biological Clocks with reference to suprachiasmatic nucleus2017

    • Author(s)
      Honma K, Honma S
    • Total Pages
      201
    • Publisher
      Hokkaido University Press
    • Related Report
      2017 Annual Research Report
  • [Book] Biological Clocks2015

    • Author(s)
      Honma S, Ono D, Enoki R, Yoshikawa T, Kuroda S and Honma K
    • Total Pages
      253
    • Publisher
      Hokkaido Univ. Press
    • Related Report
      2015 Annual Research Report
  • [Funded Workshop] Asian Forum on Chronobiology2015

    • Place of Presentation
      北海道大学学術交流会館 (北海道・札幌市)
    • Year and Date
      2015-09-07
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2023-05-26  

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