Integration of multi-oscillator circadian clock: in vivo and ex vivo imaging of clock gene expression

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390064
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: Hokkaido University
• Principal Investigator: HONMA Sato 北海道大学, 大学院・医学研究科, 特任教授 (20142713)
• Co-Investigator(Renkei-kenkyūsha): HAMADA Toshiyuki 北海道大学, 大学院・医学研究科, 特任講師 (20360208) ; NAKAMURA Tomoko (YOSHIKAWA Tomoko) 北海道大学, 大学院・医学研究科, 特任助教 (30451397) ; NISHIDE Shin-ya 北海道大学, 大学院・医学研究科, 助教 (40451398) ; ENOKI Ryosuke 北海道大学, 大学院・医学研究科, 助教 (00528341)
• Project Period (FY): 2009 – 2011
• Keywords: 生体リズム / 時計遺伝子 / イメージング / ルシフェラーゼ / 視交叉上核

Research Abstract

We aimed to clarify mutual coupling mechanisms of oscillator cells in the central circadian clock, the suprachiasmatic nucleus (SCN). We developed in vivo monitoring systems for clock gene expression from the SCN of unanesthetized and unrestrained animals and a long-term and real-time ex vivo monitoring systems for intracellular Ca++ levels from the entire neurons of cultured SCN slices. We demonstrated that all SCN neurons exhibit robust circadian rhythms in Ca++ levels which are topologically specific and the coupling between the pacemakers in the dorsal and ventral SCN depends on synaptic interaction. We further demonstrated that clock gene Cry is essential for the development of oscillator cell network in the SCN for the coherent rhythm expression which takes place around weaning period.

Research Products

• [Journal Article] Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus (2013)
  • Author(s): Ono D, Honma S, and Honma K
  • Journal Title: Nat. Comm Volume: (in press)
  • DOI: doi:10.1038/ncomms2670
  • Peer Reviewed
• [Journal Article] Fast synchronous oscillations of firing rate in cultured rat suprachiasmatic nucleus neurons:possible role in circadian synchronization in the intact nucleus (2013)
  • Author(s): Kononenko NI, Honma K and Honma S
  • Journal Title: Neurosci. Res Volume: 75 Pages: 218-227
  • DOI: doi:10.1016/j.neures.2013.01.003
  • Peer Reviewed
• [Journal Article] Daily exposure to cold phase-shifts circadian clock of neonatal rat in vivo (2013)
  • Author(s): Yoshikawa T, Matsuno A, Yamanaka Y, Nishide S, Honma S and Honma K
  • Journal Title: Eur.J.Neurosci Volume: 37 Pages: 491-497
  • DOI: doi:10.1111/ejn.12052
  • Peer Reviewed
• [Journal Article] Differential responses of circadian Per2 expression rhythms in discrete brain areas to daily injection of methamphetamine and restricted feeding in rats (2013)
  • Author(s): Natsubori A, Honnma K and Honma S
  • Journal Title: Eur.J.Neurosci Volume: 37 Pages: 251-258
  • DOI: doi:10.1111/ejn.12034
  • Peer Reviewed
• [Journal Article] Topological specificity and hierarchical network of the circadian calcium rhythm in the suprachiasmatic nucleus (2012)
  • Author(s): Enoki R, Kuroda S, Ono C, Hasan MT, Honma S, Ueda T and Honma K
  • Journal Title: Proc.Natl. Acad.Sci USA Volume: 109 Pages: 21498-21503
  • DOI: doi:10.1073/pnas.1214415110
  • Peer Reviewed
• [Journal Article] Human blood metabolite timetable indicates internal body time (2012)
  • Author(s): Kasukawa T, Sugimoto M, Hida A, Minami Y, Mori M, Honma S, Honma K, Mishima K, Soga T, Ueda HR
  • Journal Title: Proc.Natl. Acad. Sci. U.S.A Volume: 109(37) Pages: 15036-41
  • DOI: doi:10.1073/pnas.1207768109
  • Peer Reviewed
• [Journal Article] Suprachiasmatic nucleus: cellular clocks and networks (2012)
  • Author(s): Honma S, Ono D, Suzuki Y, Inagaki N, Yoshikawa T, Nakamura W and Honma K
  • Journal Title: In Progress in Brain Res Volume: 199 Pages: 129-141
  • DOI: doi:10.1016/B978-0-444-59427-3.00029-0
  • Peer Reviewed
• [Journal Article] Single-cell resolution fluorescence imaging of circadian rhythms detected with a Nipkow spinning disk confocal system (2012)
  • Author(s): Enoki R, Ono D, Hasan MT, Honma S and Honma K
  • Journal Title: J Neurosci Methods Volume: 202 Pages: 72-29
  • DOI: doi:10.1016/j.jneumeth.2012.03.004
  • Peer Reviewed
• [Journal Article] JNK regulates the photic response of the mammalian circadian clock (2012)
  • Author(s): Yoshitane H, Honma S, Imamura K, Nakajima H, Nishide S, Ono D, Kiyota H, Shinozaki N, Matsuki H, Wada N, Doi H, Hamada T, Honma K and Fukada Y
  • Journal Title: EMBO Report Volume: 13 Pages: 455-561
  • DOI: doi:10.1038/embor.2012.37
  • Peer Reviewed
• [Journal Article] Synchronized ATP oscillations have a critical role in prechondrogenic condensation during chondrogenesis (2012)
  • Author(s): Kwon HJ, Ohmiya Y, Honma K-I, Honma S, Nagai T, Saito K, and Yasuda K
  • Journal Title: Cell Death and Disease Volume: 3 Pages: e278
  • DOI: doi:10.1038/cddis.2012.20
  • Peer Reviewed
• [Journal Article] De novo synthesis of PERIOD initiates circadian oscillation in cultured mouse suprachiasmatic nucleus after prolongedinhibition of protein synthesis by cycloheximide (2012)
  • Author(s): Nishide S, Ono D, Yamada Y, Honma S and Honma K
  • Journal Title: Eur J Neurosci Volume: 35 Pages: 291-299
  • DOI: doi:10.1111/j.1460-9568.2011.07952.x
  • Peer Reviewed
• [Journal Article] Regulation of basic helix-loop-helix transcription factors Dec1 and Dec2 by RORα and their roles in adipogenesis (2012)
  • Author(s): Ozaki N, Noshiro M, Kawamoto T, Nakashima A, Honda K, Fukuzaki-Dohi U, Honma S, Fujimoto K, Tanimoto K, Tanne K and Kato, Y
  • Journal Title: Genes Cells Volume: 17 Pages: 109-21
  • Peer Reviewed
• [Journal Article] Light responsiveness of clock genes, Per1 and Per2, in the olfactory bulb of mice (2011)
  • Author(s): Hamada T, Honma S and Honma K
  • Journal Title: Biochem Biophys Res Commun Volume: 409 Pages: 727-731
  • DOI: doi:10.1016/j.bbrc.2011.05.076
  • Peer Reviewed
• [Journal Article] Physical exercise accelerates re-entrainment of human sleep-wake cycle but not of plasma melatonin rhythm to 8 h phase-advanced sleep schedule (2011)
  • Author(s): YamanakaY, Hashimoto S, Tanahashi Y, Nishide S, Honma S, and Honma K
  • Journal Title: Am J Physiol Regul Integr Comp Physiol Volume: 298 Pages: R681-691
  • DOI: doi:10.1152/ajpregu.00345
  • Peer Reviewed
• [Journal Article] Loss of circadian rhythm andlight-induced suppression of pineal melatonin levels in Cry1 and Cry2 double-deficient mice (2010)
  • Author(s): Yamanaka Y, Suzuki Y, Todo T, Honma K andHonma S
  • Journal Title: Genes to Cells Volume: 15 Pages: 1063-1071
  • DOI: doi:10.1111/j.1365-2443.2010.01443.x
  • Peer Reviewed
• [Journal Article] Multichannel perfusion culture bioluminescence reporter system for long-term detection in living cells (2010)
  • Author(s): Watanabe T, Enomoto T, Takahashi M, Honma S, Honma K, Ohmiya Y
  • Journal Title: Anal. Biochem Volume: 402 Pages: 107-109
  • DOI: doi:10.1016/j.ab.2010.03.014
  • Peer Reviewed
• [Journal Article] Self-sustained circadian rhythm in cultured humanmononuclear cells isolated from peripheral blood (2010)
  • Author(s): Ebisawa T, Numazawa K, Shimada H, IzutsubH, Sasaki T, Kato N, Tokunaga K, Akio Mori A, Honma K, Honma S, Shibata S
  • Journal Title: Neurosci Res Volume: 66 Pages: 223-227
  • DOI: doi:10.1016/j.neures.2009.10.007
  • Peer Reviewed
• [Journal Article] The liver X receptors (LXRα and LXRβ) are potent regulators for hepatic Dec1 expression (2009)
  • Author(s): Noshiro M, Usui E, Kawamoto T, Sato F, Nakashima A, Ueshima T, Honda K, Fujimoto K, Honma S, Honma K, Makishima M and Kato Y
  • Journal Title: Genes to Cells Volume: 14 Pages: 29-40
  • DOI: doi:10.1111/j.1365-2443
  • Peer Reviewed
• [Presentation] Multi-oscillator System of Mammalian Circadian Clock (2012)
  • Author(s): Honma S. Natsubori A, Honma K
  • Organizer: Symposium "Molecular and cellular mechanisms of circadian clock and sleep", Asian Society for Sleep Research
  • Place of Presentation: Taipei International Convention Center, Taiwan
  • Year and Date: 20121130-1202
• [Presentation] Monitoring the circadian clock'stick; multiple hands for multiple functions (2012)
  • Author(s): Honma S
  • Organizer: 4th International Symposium on Photonic Bioimaging
  • Place of Presentation: Hokkaido University Conference Center
  • Year and Date: 20120916-17
• [Presentation] Suprachiasmatic nucleus output couplings. Suprachiasmatic Structure Workshop (2012)
  • Author(s): Honma S
  • Organizer: Society for Research on Biological Rhythms Biannual meeting 2012
  • Place of Presentation: Sandestin Golf and Beach Resort, USA
  • Year and Date: 20120519-24
• [Presentation] Signal integration of circadian neuronal networks (2012)
  • Author(s): Honma S
  • Organizer: Society for Research on Biological Rhythms Biannual Meeting 2012
  • Place of Presentation: Sandestin Golf and Beach Resort, USA
  • Year and Date: 20120519-24
• [Presentation] Continuous monitoring of circadian clock' s tick in the suprachiasmatic neurons (2012)
  • Author(s): Honma S
  • Organizer: International Syposium on Frontiers in Sleep and Biological Rhythms' Research
  • Place of Presentation: Dokuz Eylul University Izmir,Turkey
  • Year and Date: 20120430-0502
• [Presentation] Single cell neuronal clocks and regional pacemakers in the suprachiasmatic nucleus (2011)
  • Author(s): Honma, S
  • Organizer: International Symposium on Photonic Bioimaging
  • Place of Presentation: Keio Plaza Hotel, Sapporo
  • Year and Date: 20111021-23
• [Presentation] Mammalian circadian clocks detecting morning light and evening lights (2011)
  • Author(s): Honma S, Yoshikawa T and Honma K
  • Organizer: 6th World congress of the World Sleep Federation
  • Place of Presentation: Kyoto International Conference Center, Kyoto
  • Year and Date: 20111015-20
• [Presentation] Animal models of human sleep-wake cycle: non-SCN circadian behavior rhythms in rodents (2011)
  • Author(s): Kameyama A, Honma S., Honma K
  • Organizer: 6th World congress of the World Sleep Federation
  • Place of Presentation: Kyoto International Conference Center, Kyoto
  • Year and Date: 20111015-20
• [Presentation] Effect of scheduled physical exercise on re-entrainment of human circadian rhythms to 8 h advanced sleep schedule in isolation facility (2011)
  • Author(s): Yamanaka Y, Hashimoto S, Honma S. and Honma K
  • Organizer: 6th World Congress of the World Sleep Federation
  • Place of Presentation: Kyoto International Conference Center, Kyoto
  • Year and Date: 20111015-20
• [Presentation] Suprachiasmatic nucleus: cellular clocks and networks (2011)
  • Author(s): Honma S
  • Organizer: 12th Congress of European Society for Biological Rhythm
  • Place of Presentation: Oxford, UK
  • Year and Date: 20110820-26
• [Presentation] Network vs single neuronal rhythms in the SCN. (2011)
  • Author(s): Honma S
  • Organizer: Symposium:Molecular and network properties of the suprachiasmatic nucleus, the 3rd World Congress of Chronobiology
  • Place of Presentation: Cultural Center BUAP, Puebra, Mexico
  • Year and Date: 20110505-09
• [Presentation] Cellular rhythms and oscillatory networks in the suprachiasmatic nucleus (2011)
  • Author(s): Honma S
  • Organizer: Workshop: Emergence of circadian rhythms from the central pacemaker and beyond
  • Place of Presentation: Institute of Theoretical Biology, Humboldt University, Germany
  • Year and Date: 2011-08-15
• [Presentation] Panel Discussion "Neurophysiology and humoral regulation of sleep" (2010)
  • Author(s): Honma S. and Honma K. Animal model of human sleep-wake rhythm
  • Organizer: The 11th Congress of Turkish Sleep Society
  • Place of Presentation: Maritim Pine Beach Resort, Antalya, Turkey
  • Year and Date: 20101106-10
• [Presentation] Assessing multi-oscillator mammalian clock using mice with clock gene mutation (2010)
  • Author(s): Honma S
  • Organizer: Lorenz Center Workshop, Assembling multi-cellular Circadian Pacemaker
  • Place of Presentation: Lorenz Center, Leiden, The Netherlands
  • Year and Date: 20100816-20
• [Presentation] Rapid shift of social schedule induces an internal desynchronization between sleep-wake cycle and plasma melatonin rhythms (2009)
  • Author(s): Yamanaka Y, Hashimoto S, Nakamura K, Tanahashi Y, Nishide S, Yamada Y, Honma S and Honma
  • Organizer: The 1st ASRS Summit and Symposium of Asia Oceania Sleep Research and Sleep
  • Place of Presentation: Medicine in Okinawa Bankoku Sniryokan, Okinawa
  • Year and Date: 20091030-1101
• [Presentation] Seasonality in sleep and wakefulness (2009)
  • Author(s): Honma S, Yoshikawa T, and Honma,K
  • Organizer: The6th Congress of Asian Sleep Research Society
  • Place of Presentation: Osaka Convention Center, Osakka
  • Year and Date: 20091024-27
• [Presentation] Circadian firing rhythms in Cry1/Cry2 double-deficient mice in the cultured suprachiasmatic nucleus (2009)
  • Author(s): Ono D, Honma S, and Honma K
  • Organizer: IXth European Congress on Biological Rhythms, Univ
  • Place of Presentation: Strasbourg, Strasbourg, France
  • Year and Date: 20090822-28
• [Presentation] Nonphotic time cues phase-dependently accelerate phase-shifts of mouse peripheral clocks (2009)
  • Author(s): Yamanaka Y, Honma S, and Honma K
  • Organizer: IXth European Congress on Biological Rhythms, Univ
  • Place of Presentation: Strasbourg, Strasbourg, France
  • Year and Date: 20090822-28
• [Presentation] Non-photic time cues and animal life: photic cue is not almighty. IXth European Congress on Biological Rhythms, Univ (2009)
  • Author(s): Honma S
  • Organizer: Strasbourg
  • Place of Presentation: Strasbourg, France
  • Year and Date: 20090822-28
• [Presentation] Clock for all seasons composed of functionally heterogenous SCN cells (2009)
  • Author(s): Honma S. Yoshikawa T, and Honma,K
  • Organizer: International Symposium on Biological Rhythms
  • Place of Presentation: Hokkaido University Conference Hall, Sapporo
  • Year and Date: 20090801-04
• [Presentation] Clock mechanisms in mammals encoding photoperiods (2009)
  • Author(s): Honma S, Yoshikawa T, Tokumaru N, and Honma,K
  • Organizer: IUPS 2009
  • Place of Presentation: Kyoto International Conference Center, Kyoto
  • Year and Date: 20090728-0801
• [Presentation] Photic regulation of phase and tau; adaptive role of a kinase in the SCN (2009)
  • Author(s): Honma S
  • Organizer: Gordon Conference on Chronobiology, Salve Regina Collage
  • Place of Presentation: New Port, USA
  • Year and Date: 20090719-24
• [Presentation] Bioluminescence imaging for assessing heterogeneous cell functions in the central circadian clock (2009)
  • Author(s): Honma S
  • Organizer: the 3rd Symposium for Research Center for Cooperative Projects of Hokkaido University Graduate School of Medicine, Hokkaido Univ
  • Place of Presentation: Conference Center, Sapporo
  • Year and Date: 20090313-14
• [Book] 中枢時計の分子生物学 DOJIN SCIENCE SERIES 02「時間生物学」 (2012)
  • Author(s): 本間さと
  • Total Pages: 55-65
  • Publisher: 海老原史樹文、吉村崇(編)化学同人
• [Book] 嗅球の体内時計と嗅覚刺激の作用、体内時計の科学と産業応用 (2011)
  • Author(s): 浜田俊幸、本間さと、本間研一
  • Total Pages: 117-124
  • Publisher: 柴田重信監修、シーエムシー出版
• [Book] Tamaki N. Kuge Y eds "Molecular Imaging for Integrated Medical Therapy and Drug Development" Springer, Tokyo (2010)
  • Author(s): Honma S, Yoshikawa T, Nishide S, Ono D and Honma K
  • Total Pages: 189-196
  • Publisher: Bioluminescent imaging for assessing heterogeneous cell functions in the mammalian central circadian clock
• [Book] 環境応答-概日リズムからだと光の事典 (2010)
  • Author(s): 本間さと
  • Total Pages: 281-285
  • Publisher: 太陽紫外線防御研究委員会編集朝倉書店
• [Book] Editor-in-Chief: LR. Squire, New Encyclopedia of Neuroscience, Elsevier (2009)
  • Author(s): Honma S and Honma K
  • Total Pages: 843-847
  • Publisher: Single cell neuronal circadian clocks
• [Book] 視交叉上核と光周性光周性の分子生物学 (2009)
  • Author(s): 吉川朋子、本間さと
  • Total Pages: 159-168
  • Publisher: 海老原史樹文,伊澤毅編シュプリンガー・ジャパン、東京
• [Remarks]
  • URL: http://www.hucc.hokudai.ac.jp/~a10071/
• [Patent(Industrial Property Rights)] ターゲット位置追跡装置およびターゲット発光検出装置 (2010)
  • Inventor(s): 石川正純、浜田俊幸、本間研一、本間さと、ケネス・リー・サザーランド
  • Industrial Property Rights Holder: 北海道大学
  • Industrial Property Number: 特許、特願2010-245624
  • Filing Date: 2010-11-01