Period coding of Bmal1 oscillators in the suprachiasmatic nucleus

J. Myung, S. Hong, F. Hatanaka, Y. Nakajima, E. De Schutter, T. Takumi

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Circadian oscillators in the suprachiasmatic nucleus (SCN) collectively orchestrate 24 h rhythms in the body while also coding for seasonal rhythms. Although synchronization is required among SCN oscillators to provide robustness for regular timekeeping (Herzog et al., 2004), heterogeneity of period and phase distributions is needed to accommodate seasonal variations in light duration (Pittendrigh and Daan, 1976b). In the mouse SCN, the heterogeneous phase distribution has been recently found in the cycling of clock genes Period 1 and Period 2 (Per1, Per2) and has been shown to reorganize by relative day lengths (Inagaki et al., 2007). However, it is not yet clearly understood what underlies the spatial patterning of Per1 and Per2 expression (Yamaguchi et al., 2003; Foley et al., 2011) and its plasticity. We found that the period of the oscillation in Bmal1 expression, a positive-feedback component of the circadian clock, preserves the behavioral circadian period under culture and drives clustered oscillations in the mouse SCN. Pharmacological and physical isolations of SCN subregions indicate that the period of Bmal1 oscillation is subregion specific and is preserved during culture. Together with computer simulations, we show that either the intercellular coupling does not strongly influence the Bmal1 oscillation or the nature of the coupling is more complex than previously assumed. Furthermore, we have found that the region-specific periods are modulated by the light conditions that an animal is exposed to. Based on these, we suggest that the period forms the basis of seasonal coding in the SCN. © 2012 the authors.
Original languageEnglish
Pages (from-to)8900-8918
Number of pages19
JournalJournal of Neuroscience
Volume32
Issue number26
DOIs
Publication statusPublished - 2012
Externally publishedYes

Fingerprint

Suprachiasmatic Nucleus
Light
Circadian Clocks
Computer Simulation
Pharmacology
Genes

Keywords

  • PER2 protein
  • protein BMAL1
  • animal experiment
  • animal tissue
  • article
  • bioluminescence
  • circadian rhythm
  • computer simulation
  • female
  • immunofluorescence
  • immunohistochemistry
  • light dark cycle
  • locomotion
  • male
  • mouse
  • nonbiological model
  • nonhuman
  • plasticity
  • priority journal
  • protein expression
  • suprachiasmatic nucleus
  • transgenic mouse
  • Action Potentials
  • Animals
  • ARNTL Transcription Factors
  • Biological Clocks
  • Brain Mapping
  • Circadian Rhythm
  • Cluster Analysis
  • GABA Antagonists
  • Gene Expression Regulation
  • Luminescent Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Neurological
  • Motor Activity
  • Neurons
  • Nonlinear Dynamics
  • Organ Culture Techniques
  • Period Circadian Proteins
  • Photoperiod
  • Pyridazines
  • Sodium Channel Blockers
  • Software
  • Statistics as Topic
  • Suprachiasmatic Nucleus
  • Tetrodotoxin

Cite this

Myung, J., Hong, S., Hatanaka, F., Nakajima, Y., De Schutter, E., & Takumi, T. (2012). Period coding of Bmal1 oscillators in the suprachiasmatic nucleus. Journal of Neuroscience, 32(26), 8900-8918. https://doi.org/10.1523/JNEUROSCI.5586-11.2012

Period coding of Bmal1 oscillators in the suprachiasmatic nucleus. / Myung, J.; Hong, S.; Hatanaka, F.; Nakajima, Y.; De Schutter, E.; Takumi, T.

In: Journal of Neuroscience, Vol. 32, No. 26, 2012, p. 8900-8918.

Research output: Contribution to journalArticle

Myung, J, Hong, S, Hatanaka, F, Nakajima, Y, De Schutter, E & Takumi, T 2012, 'Period coding of Bmal1 oscillators in the suprachiasmatic nucleus', Journal of Neuroscience, vol. 32, no. 26, pp. 8900-8918. https://doi.org/10.1523/JNEUROSCI.5586-11.2012
Myung, J. ; Hong, S. ; Hatanaka, F. ; Nakajima, Y. ; De Schutter, E. ; Takumi, T. / Period coding of Bmal1 oscillators in the suprachiasmatic nucleus. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 26. pp. 8900-8918.
@article{c77652334e4e485b9bbc5c4e0250dab4,
title = "Period coding of Bmal1 oscillators in the suprachiasmatic nucleus",
abstract = "Circadian oscillators in the suprachiasmatic nucleus (SCN) collectively orchestrate 24 h rhythms in the body while also coding for seasonal rhythms. Although synchronization is required among SCN oscillators to provide robustness for regular timekeeping (Herzog et al., 2004), heterogeneity of period and phase distributions is needed to accommodate seasonal variations in light duration (Pittendrigh and Daan, 1976b). In the mouse SCN, the heterogeneous phase distribution has been recently found in the cycling of clock genes Period 1 and Period 2 (Per1, Per2) and has been shown to reorganize by relative day lengths (Inagaki et al., 2007). However, it is not yet clearly understood what underlies the spatial patterning of Per1 and Per2 expression (Yamaguchi et al., 2003; Foley et al., 2011) and its plasticity. We found that the period of the oscillation in Bmal1 expression, a positive-feedback component of the circadian clock, preserves the behavioral circadian period under culture and drives clustered oscillations in the mouse SCN. Pharmacological and physical isolations of SCN subregions indicate that the period of Bmal1 oscillation is subregion specific and is preserved during culture. Together with computer simulations, we show that either the intercellular coupling does not strongly influence the Bmal1 oscillation or the nature of the coupling is more complex than previously assumed. Furthermore, we have found that the region-specific periods are modulated by the light conditions that an animal is exposed to. Based on these, we suggest that the period forms the basis of seasonal coding in the SCN. {\circledC} 2012 the authors.",
keywords = "PER2 protein, protein BMAL1, animal experiment, animal tissue, article, bioluminescence, circadian rhythm, computer simulation, female, immunofluorescence, immunohistochemistry, light dark cycle, locomotion, male, mouse, nonbiological model, nonhuman, plasticity, priority journal, protein expression, suprachiasmatic nucleus, transgenic mouse, Action Potentials, Animals, ARNTL Transcription Factors, Biological Clocks, Brain Mapping, Circadian Rhythm, Cluster Analysis, GABA Antagonists, Gene Expression Regulation, Luminescent Proteins, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Neurological, Motor Activity, Neurons, Nonlinear Dynamics, Organ Culture Techniques, Period Circadian Proteins, Photoperiod, Pyridazines, Sodium Channel Blockers, Software, Statistics as Topic, Suprachiasmatic Nucleus, Tetrodotoxin",
author = "J. Myung and S. Hong and F. Hatanaka and Y. Nakajima and {De Schutter}, E. and T. Takumi",
note = "引用次數:32 Export Date: 18 September 2018 CODEN: JNRSD 通訊地址: Takumi, T.; Laboratory of Integrative Bioscience, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami, Hiroshima 734-8553, Japan; 電子郵件: takumi@hiroshima-u.ac.jp 化學物質/CAS: ARNTL Transcription Factors; Arntl protein, mouse; GABA Antagonists; Luminescent Proteins; Period Circadian Proteins; Pyridazines; Sodium Channel Blockers; Tetrodotoxin, 4368-28-9; gabazine, 104104-50-9 參考文獻: Abraham, U., Granada, A.E., Westermark, P.O., Heine, M., Kramer, A., Herzel, H., Coupling governs entrainment range of circadian clocks (2010) Mol Syst Biol, 6, p. 438; Akman, O.E., Rand, D.A., Brown, P.E., Millar, A.J., Robustness from flexibility in the fungal circadian clock (2010) BMC Syst Biol, 4, p. 88; Azran, A., Ghahramani, Z., (2006) Spectral Methods For Automatic Multiscale Data Clustering, , Paper presented at Computer Vision and Pattern Recognition: 2006 IEEE Computer Society Conference on Computer Vision and Pattern Recognition, New York, June; Belle, M.D., Diekman, C.O., Forger, D.B., Piggins, H.D., Daily electrical silencing in the mammalian circadian clock (2009) Science, 326, pp. 281-284; Brown, T.M., Piggins, H.D., Spatiotemporal heterogeneity in the electrical activity of suprachiasmatic nuclei neurons and their response to photoperiod (2009) J Biol Rhythms, 24, pp. 44-54; Buhr, E.D., Yoo, S.H., Takahashi, J.S., Temperature as a universal resetting cue for mammalian circadian oscillators (2010) Science, 330, pp. 379-385; Butler, M.P., Silver, R., Basis of robustness and resilience in the suprachiasmatic nucleus: Individual neurons form nodes in circuits that cycle daily (2009) J Biol Rhythms, 24, pp. 340-352; de Moortel, I., Munday, S.A., Hood, A.W., Wavelet analysis: The effect of varying basic wavelet parameters (2004) Solar Phys, 222, pp. 203-237; Ermentrout, G.B., Kopell, N., Frequency plateaus in a chain of weakly coupled oscillators. 1 (1984) SIAM J Math Anal, 15, pp. 215-237; Evans, J.A., Leise, T.L., Castanon-Cervantes, O., Davidson, A.J., Intrinsic regulation of spatiotemporal organization within the suprachiasmatic nucleus (2011) PLoS One, 6, pp. e15869; Foley, N.C., Tong, T.Y., Foley, D., Lesauter, J., Welsh, D.K., Silver, R., Characterization of orderly spatiotemporal patterns of clock gene activation in mammalian suprachiasmatic nucleus (2011) Eur J Neurosci, 33, pp. 1851-1865; Fukuda, H., Tokuda, I., Hashimoto, S., Hayasaka, N., Quantitative analysis of phase wave of gene expression in the mammalian central circadian clock network (2011) PLoS One, 6, pp. e23568; Gonze, D., Bernard, S., Waltermann, C., Kramer, A., Herzel, H., Spontaneous synchronization of coupled circadian oscillators (2005) Biophys J, 89, pp. 120-129; Goutte, C., Toft, P., Rostrup, E., Nielsen, F., Hansen, L.K., On clustering fMRI time series (1999) Neuroimage, 9, pp. 298-310; Guilding, C., Hughes, A.T., Brown, T.M., Namvar, S., Piggins, H.D., A riot of rhythms: Neuronal and glial circadian oscillators in the mediobasal hypothalamus (2009) Mol Brain, 2, p. 28; Does the morning and evening oscillator model fit better for flies or mice? (2009) J Biol Rhythms, 24, pp. 259-270. , Helfrich-F{\"o}rster C; Herzog, E.D., Aton, S.J., Numano, R., Sakaki, Y., Tei, H., Temporal precision in the mammalian circadian system: A reliable clock from less reliable neurons (2004) J Biol Rhythms, 19, pp. 35-46; Inagaki, N., Honma, S., Ono, D., Tanahashi, Y., Honma, K., Separate oscillating cell groups in mouse suprachiasmatic nucleus couple photoperiodically to the onset and end of daily activity (2007) Proc Natl Acad Sci U S A, 104, pp. 7664-7669; Klein, D.C., Moore, R.Y., Reppert, S.M., Suprachiasmatic nucleus: The mind's clock (1991), New York: Oxford UP; Ko, C.H., Yamada, Y.R., Welsh, D.K., Buhr, E.D., Liu, A.C., Zhang, E.E., Ralph, M.R., Takahashi, J.S., Emergence of noise-induced oscillations in the central circadian pacemaker (2010) PLoS Biol, 8, pp. e1000513; Kuramoto, Y., (1984) Chemical Oscillations, Waves, and Turbulence, , New York: Springer; Meeker, K., Harang, R., Webb, A.B., Welsh, D.K., Doyle III, F.J., Bonnet, G., Herzog, E.D., Petzold, L.R., Wavelet measurement suggests cause of period instability in mammalian circadian neurons (2011) J Biol Rhythms, 26, pp. 353-362; Meng, Q.J., Maywood, E.S., Bechtold, D.A., Lu, W.Q., Li, J., Gibbs, J.E., Dupr{\'e}, S.M., Loudon, A.S., Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes (2010) Proc Natl Acad Sci U S A, 107, pp. 15240-15245; Mickman, C.T., Stubblefield, J.S., Harrington, M.E., Nelson, D.E., Photoperiod alters phase difference between activity onset in vivo and mPer2::Luc peak in vitro (2008) Am J Physiol Regul Integr Comp Physiol, 295, pp. R1688-R1694; Morin, L.P., Allen, C.N., The circadian visual system, 2005 (2006) Brain Res Rev, 51, pp. 1-60; Naito, E., Watanabe, T., Tei, H., Yoshimura, T., Ebihara, S., Reorganization of the suprachiasmatic nucleus coding for day length (2008) J Biol Rhythms, 23, pp. 140-149; Nakajima, Y., Yamazaki, T., Nishii, S., Noguchi, T., Hoshino, H., Niwa, K., Viviani, V.R., Ohmiya, Y., Enhanced beetle luciferase for high-resolution bioluminescence imaging (2010) PLoS One, 5, pp. e10011; Noguchi, T., Michihata, T., Nakamura, W., Takumi, T., Shimizu, R., Yamamoto, M., Ikeda, M., Nakajima, Y., Dual-color luciferase mouse directly demonstrates coupled expression of two clock genes (2010) Biochemistry, 49, pp. 8053-8061; Ohta, H., Yamazaki, S., McMahon, D.G., Constant light desynchronizes mammalian clock neurons (2005) Nat Neurosci, 8, pp. 267-269; Pennartz, C.M., Bierlaagh, M.A., Geurtsen, A.M., Cellular mechanisms underlying spontaneous firing in rat suprachiasmatic nucleus: Involvement of a slowly inactivating component of sodium current (1997) J Neurophysiol, 78, pp. 1811-1825; Pikovsky, A., Rosenblum, M., Kurths, J., (2001) Synchronization: A Universal Concept In Nonlinear Sciences, , Cambridge, UK: Cambridge UP; Pittendrigh, C.S., Circadian rhythms and the circadian organization of living systems (1960) Cold Spring Harb Symp Quant Biol, 25, pp. 159-184; Pittendrigh, C.S., Daan, S., A functional analysis of circadian pacemakers in nocturnal rodents. I. The stability and lability of spontaneous frequency (1976) J Comp Physiol, 106, pp. 223-252; Pittendrigh, C.S., Daan, S., A functional analysis of circadian pacemakers in nocturnal rodents. V. Pacemaker structure: A clock for all seasons (1976) J Comp Physiol, 106, pp. 333-355; Quintero, J.E., Kuhlman, S.J., McMahon, D.G., The biological clock nucleus: A multiphasic oscillator network regulated by light (2003) J Neurosci, 23, pp. 8070-8076; Rel{\'o}gio, A., Westermark, P.O., Wallach, T., Schellenberg, K., Kramer, A., Herzel, H., Tuning the mammalian circadian clock: Robust synergy of two loops (2011) PLoS Comput Biol, 7, pp. e1002309; Reppert, S.M., Weaver, D.R., Coordination of circadian timing in mammals (2002) Nature, 418, pp. 935-941; Schaap, J., Albus, H., Vanderleest, H.T., Eilers, P.H., D{\'e}t{\'a}ri, L., Meijer, J.H., Heterogeneity of rhythmic suprachiasmatic nucleus neurons: Implications for circadian waveform and photoperiodic encoding (2003) Proc Natl Acad Sci U S A, 100, pp. 15994-15999; Schwartz, W.J., Gross, R.A., Morton, M.T., The suprachiasmatic nuclei contain a tetrodotoxin-resistant circadian pacemaker (1987) Proc Natl Acad Sci U S A, 84, pp. 1694-1698; Silver, R., Lehman, M.N., Gibson, M., Gladstone, W.R., Bittman, E.L., Dispersed cell suspensions of fetal SCNrestore circadian rhythmicity in SCNlesioned adult hamsters (1990) Brain Res, 525, pp. 45-58; Small, M., (2005) Applied Nonlinear Time Series Analysis: Applications In Physics, Physiology and Finance, , London: World Scientific; Stoleru, D., Nawathean, P., Fern{\'a}ndez, M.P., Menet, J.S., Ceriani, M.F., Rosbash, M., The Drosophila circadian network is a seasonal timer (2007) Cell, 129, pp. 207-219; Vanderleest, H.T., Houben, T., Michel, S., Deboer, T., Albus, H., Vansteensel, M.J., Block, G.D., Meijer, J.H., Seasonal encoding by the circadian pacemaker of the SCN (2007) Curr Biol, 17, pp. 468-473; von Gall, C., Noton, E., Lee, C., Weaver, D.R., Light does not degrade the constitutively expressed BMAL1 protein in the mouse suprachiasmatic nucleus (2003) Eur J Neurosci, 18, pp. 125-133; von Luxburg, U., A tutorial on spectral clustering (2006) Stat Comput, 17, pp. 395-416; Ward, J.H., Hierarchical grouping to optimize an objective function (1963) J Am Stat Assoc, 58, pp. 236-244; Webb, A.B., Angelo, N., Huettner, J.E., Herzog, E.D., Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons (2009) Proc Natl Acad Sci U S A, 106, pp. 16493-16498; Welsh, D.K., Logothetis, D.E., Meister, M., Reppert, S.M., Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms (1995) Neuron, 14, pp. 697-706; Welsh, D.K., Yoo, S.H., Liu, A.C., Takahashi, J.S., Kay, S.A., Bioluminescence imaging of individual fibroblasts reveals persistent, independently phased circadian rhythms of clock gene expression (2004) Curr Biol, 14, pp. 2289-2295; Winfree, A.T., Biological rhythms and the behavior of populations of coupled oscillators (1967) J Theor Biol, 16, pp. 15-42; Yamaguchi, S., Isejima, H., Matsuo, T., Okura, R., Yagita, K., Kobayashi, M., Okamura, H., Synchronization of cellular clocks in the suprachiasmatic nucleus (2003) Science, 302, pp. 1408-1412; Yan, L., Karatsoreos, I., Lesauter, J., Welsh, D.K., Kay, S., Foley, D., Silver, R., Exploring spatiotemporal organization of SCNcircuits (2007) Cold Spring Harb Symp Quant Biol, 72, pp. 527-541; Yoo, S.H., Yamazaki, S., Lowrey, P.L., Shimomura, K., Ko, C.H., Buhr, E.D., Siepka, S.M., Takahashi, J.S., PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues (2004) Proc Natl Acad Sci U S A, 101, pp. 5339-5346; Yoshii, T., W{\"u}lbeck, C., Sehadova, H., Veleri, S., Bichler, D., Stanewsky, R., Helfrich-F{\"o}rster, C., The neuropeptide pigment-dispersing factor adjusts period and phase of Drosophila's clock (2009) J Neurosci, 29, pp. 2597-2610",
year = "2012",
doi = "10.1523/JNEUROSCI.5586-11.2012",
language = "English",
volume = "32",
pages = "8900--8918",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "26",

}

TY - JOUR

T1 - Period coding of Bmal1 oscillators in the suprachiasmatic nucleus

AU - Myung, J.

AU - Hong, S.

AU - Hatanaka, F.

AU - Nakajima, Y.

AU - De Schutter, E.

AU - Takumi, T.

N1 - 引用次數:32 Export Date: 18 September 2018 CODEN: JNRSD 通訊地址: Takumi, T.; Laboratory of Integrative Bioscience, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami, Hiroshima 734-8553, Japan; 電子郵件: takumi@hiroshima-u.ac.jp 化學物質/CAS: ARNTL Transcription Factors; Arntl protein, mouse; GABA Antagonists; Luminescent Proteins; Period Circadian Proteins; Pyridazines; Sodium Channel Blockers; Tetrodotoxin, 4368-28-9; gabazine, 104104-50-9 參考文獻: Abraham, U., Granada, A.E., Westermark, P.O., Heine, M., Kramer, A., Herzel, H., Coupling governs entrainment range of circadian clocks (2010) Mol Syst Biol, 6, p. 438; Akman, O.E., Rand, D.A., Brown, P.E., Millar, A.J., Robustness from flexibility in the fungal circadian clock (2010) BMC Syst Biol, 4, p. 88; Azran, A., Ghahramani, Z., (2006) Spectral Methods For Automatic Multiscale Data Clustering, , Paper presented at Computer Vision and Pattern Recognition: 2006 IEEE Computer Society Conference on Computer Vision and Pattern Recognition, New York, June; Belle, M.D., Diekman, C.O., Forger, D.B., Piggins, H.D., Daily electrical silencing in the mammalian circadian clock (2009) Science, 326, pp. 281-284; Brown, T.M., Piggins, H.D., Spatiotemporal heterogeneity in the electrical activity of suprachiasmatic nuclei neurons and their response to photoperiod (2009) J Biol Rhythms, 24, pp. 44-54; Buhr, E.D., Yoo, S.H., Takahashi, J.S., Temperature as a universal resetting cue for mammalian circadian oscillators (2010) Science, 330, pp. 379-385; Butler, M.P., Silver, R., Basis of robustness and resilience in the suprachiasmatic nucleus: Individual neurons form nodes in circuits that cycle daily (2009) J Biol Rhythms, 24, pp. 340-352; de Moortel, I., Munday, S.A., Hood, A.W., Wavelet analysis: The effect of varying basic wavelet parameters (2004) Solar Phys, 222, pp. 203-237; Ermentrout, G.B., Kopell, N., Frequency plateaus in a chain of weakly coupled oscillators. 1 (1984) SIAM J Math Anal, 15, pp. 215-237; Evans, J.A., Leise, T.L., Castanon-Cervantes, O., Davidson, A.J., Intrinsic regulation of spatiotemporal organization within the suprachiasmatic nucleus (2011) PLoS One, 6, pp. e15869; Foley, N.C., Tong, T.Y., Foley, D., Lesauter, J., Welsh, D.K., Silver, R., Characterization of orderly spatiotemporal patterns of clock gene activation in mammalian suprachiasmatic nucleus (2011) Eur J Neurosci, 33, pp. 1851-1865; Fukuda, H., Tokuda, I., Hashimoto, S., Hayasaka, N., Quantitative analysis of phase wave of gene expression in the mammalian central circadian clock network (2011) PLoS One, 6, pp. e23568; Gonze, D., Bernard, S., Waltermann, C., Kramer, A., Herzel, H., Spontaneous synchronization of coupled circadian oscillators (2005) Biophys J, 89, pp. 120-129; Goutte, C., Toft, P., Rostrup, E., Nielsen, F., Hansen, L.K., On clustering fMRI time series (1999) Neuroimage, 9, pp. 298-310; Guilding, C., Hughes, A.T., Brown, T.M., Namvar, S., Piggins, H.D., A riot of rhythms: Neuronal and glial circadian oscillators in the mediobasal hypothalamus (2009) Mol Brain, 2, p. 28; Does the morning and evening oscillator model fit better for flies or mice? (2009) J Biol Rhythms, 24, pp. 259-270. , Helfrich-Förster C; Herzog, E.D., Aton, S.J., Numano, R., Sakaki, Y., Tei, H., Temporal precision in the mammalian circadian system: A reliable clock from less reliable neurons (2004) J Biol Rhythms, 19, pp. 35-46; Inagaki, N., Honma, S., Ono, D., Tanahashi, Y., Honma, K., Separate oscillating cell groups in mouse suprachiasmatic nucleus couple photoperiodically to the onset and end of daily activity (2007) Proc Natl Acad Sci U S A, 104, pp. 7664-7669; Klein, D.C., Moore, R.Y., Reppert, S.M., Suprachiasmatic nucleus: The mind's clock (1991), New York: Oxford UP; Ko, C.H., Yamada, Y.R., Welsh, D.K., Buhr, E.D., Liu, A.C., Zhang, E.E., Ralph, M.R., Takahashi, J.S., Emergence of noise-induced oscillations in the central circadian pacemaker (2010) PLoS Biol, 8, pp. e1000513; Kuramoto, Y., (1984) Chemical Oscillations, Waves, and Turbulence, , New York: Springer; Meeker, K., Harang, R., Webb, A.B., Welsh, D.K., Doyle III, F.J., Bonnet, G., Herzog, E.D., Petzold, L.R., Wavelet measurement suggests cause of period instability in mammalian circadian neurons (2011) J Biol Rhythms, 26, pp. 353-362; Meng, Q.J., Maywood, E.S., Bechtold, D.A., Lu, W.Q., Li, J., Gibbs, J.E., Dupré, S.M., Loudon, A.S., Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes (2010) Proc Natl Acad Sci U S A, 107, pp. 15240-15245; Mickman, C.T., Stubblefield, J.S., Harrington, M.E., Nelson, D.E., Photoperiod alters phase difference between activity onset in vivo and mPer2::Luc peak in vitro (2008) Am J Physiol Regul Integr Comp Physiol, 295, pp. R1688-R1694; Morin, L.P., Allen, C.N., The circadian visual system, 2005 (2006) Brain Res Rev, 51, pp. 1-60; Naito, E., Watanabe, T., Tei, H., Yoshimura, T., Ebihara, S., Reorganization of the suprachiasmatic nucleus coding for day length (2008) J Biol Rhythms, 23, pp. 140-149; Nakajima, Y., Yamazaki, T., Nishii, S., Noguchi, T., Hoshino, H., Niwa, K., Viviani, V.R., Ohmiya, Y., Enhanced beetle luciferase for high-resolution bioluminescence imaging (2010) PLoS One, 5, pp. e10011; Noguchi, T., Michihata, T., Nakamura, W., Takumi, T., Shimizu, R., Yamamoto, M., Ikeda, M., Nakajima, Y., Dual-color luciferase mouse directly demonstrates coupled expression of two clock genes (2010) Biochemistry, 49, pp. 8053-8061; Ohta, H., Yamazaki, S., McMahon, D.G., Constant light desynchronizes mammalian clock neurons (2005) Nat Neurosci, 8, pp. 267-269; Pennartz, C.M., Bierlaagh, M.A., Geurtsen, A.M., Cellular mechanisms underlying spontaneous firing in rat suprachiasmatic nucleus: Involvement of a slowly inactivating component of sodium current (1997) J Neurophysiol, 78, pp. 1811-1825; Pikovsky, A., Rosenblum, M., Kurths, J., (2001) Synchronization: A Universal Concept In Nonlinear Sciences, , Cambridge, UK: Cambridge UP; Pittendrigh, C.S., Circadian rhythms and the circadian organization of living systems (1960) Cold Spring Harb Symp Quant Biol, 25, pp. 159-184; Pittendrigh, C.S., Daan, S., A functional analysis of circadian pacemakers in nocturnal rodents. I. The stability and lability of spontaneous frequency (1976) J Comp Physiol, 106, pp. 223-252; Pittendrigh, C.S., Daan, S., A functional analysis of circadian pacemakers in nocturnal rodents. V. Pacemaker structure: A clock for all seasons (1976) J Comp Physiol, 106, pp. 333-355; Quintero, J.E., Kuhlman, S.J., McMahon, D.G., The biological clock nucleus: A multiphasic oscillator network regulated by light (2003) J Neurosci, 23, pp. 8070-8076; Relógio, A., Westermark, P.O., Wallach, T., Schellenberg, K., Kramer, A., Herzel, H., Tuning the mammalian circadian clock: Robust synergy of two loops (2011) PLoS Comput Biol, 7, pp. e1002309; Reppert, S.M., Weaver, D.R., Coordination of circadian timing in mammals (2002) Nature, 418, pp. 935-941; Schaap, J., Albus, H., Vanderleest, H.T., Eilers, P.H., Détári, L., Meijer, J.H., Heterogeneity of rhythmic suprachiasmatic nucleus neurons: Implications for circadian waveform and photoperiodic encoding (2003) Proc Natl Acad Sci U S A, 100, pp. 15994-15999; Schwartz, W.J., Gross, R.A., Morton, M.T., The suprachiasmatic nuclei contain a tetrodotoxin-resistant circadian pacemaker (1987) Proc Natl Acad Sci U S A, 84, pp. 1694-1698; Silver, R., Lehman, M.N., Gibson, M., Gladstone, W.R., Bittman, E.L., Dispersed cell suspensions of fetal SCNrestore circadian rhythmicity in SCNlesioned adult hamsters (1990) Brain Res, 525, pp. 45-58; Small, M., (2005) Applied Nonlinear Time Series Analysis: Applications In Physics, Physiology and Finance, , London: World Scientific; Stoleru, D., Nawathean, P., Fernández, M.P., Menet, J.S., Ceriani, M.F., Rosbash, M., The Drosophila circadian network is a seasonal timer (2007) Cell, 129, pp. 207-219; Vanderleest, H.T., Houben, T., Michel, S., Deboer, T., Albus, H., Vansteensel, M.J., Block, G.D., Meijer, J.H., Seasonal encoding by the circadian pacemaker of the SCN (2007) Curr Biol, 17, pp. 468-473; von Gall, C., Noton, E., Lee, C., Weaver, D.R., Light does not degrade the constitutively expressed BMAL1 protein in the mouse suprachiasmatic nucleus (2003) Eur J Neurosci, 18, pp. 125-133; von Luxburg, U., A tutorial on spectral clustering (2006) Stat Comput, 17, pp. 395-416; Ward, J.H., Hierarchical grouping to optimize an objective function (1963) J Am Stat Assoc, 58, pp. 236-244; Webb, A.B., Angelo, N., Huettner, J.E., Herzog, E.D., Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons (2009) Proc Natl Acad Sci U S A, 106, pp. 16493-16498; Welsh, D.K., Logothetis, D.E., Meister, M., Reppert, S.M., Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms (1995) Neuron, 14, pp. 697-706; Welsh, D.K., Yoo, S.H., Liu, A.C., Takahashi, J.S., Kay, S.A., Bioluminescence imaging of individual fibroblasts reveals persistent, independently phased circadian rhythms of clock gene expression (2004) Curr Biol, 14, pp. 2289-2295; Winfree, A.T., Biological rhythms and the behavior of populations of coupled oscillators (1967) J Theor Biol, 16, pp. 15-42; Yamaguchi, S., Isejima, H., Matsuo, T., Okura, R., Yagita, K., Kobayashi, M., Okamura, H., Synchronization of cellular clocks in the suprachiasmatic nucleus (2003) Science, 302, pp. 1408-1412; Yan, L., Karatsoreos, I., Lesauter, J., Welsh, D.K., Kay, S., Foley, D., Silver, R., Exploring spatiotemporal organization of SCNcircuits (2007) Cold Spring Harb Symp Quant Biol, 72, pp. 527-541; Yoo, S.H., Yamazaki, S., Lowrey, P.L., Shimomura, K., Ko, C.H., Buhr, E.D., Siepka, S.M., Takahashi, J.S., PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues (2004) Proc Natl Acad Sci U S A, 101, pp. 5339-5346; Yoshii, T., Wülbeck, C., Sehadova, H., Veleri, S., Bichler, D., Stanewsky, R., Helfrich-Förster, C., The neuropeptide pigment-dispersing factor adjusts period and phase of Drosophila's clock (2009) J Neurosci, 29, pp. 2597-2610

PY - 2012

Y1 - 2012

N2 - Circadian oscillators in the suprachiasmatic nucleus (SCN) collectively orchestrate 24 h rhythms in the body while also coding for seasonal rhythms. Although synchronization is required among SCN oscillators to provide robustness for regular timekeeping (Herzog et al., 2004), heterogeneity of period and phase distributions is needed to accommodate seasonal variations in light duration (Pittendrigh and Daan, 1976b). In the mouse SCN, the heterogeneous phase distribution has been recently found in the cycling of clock genes Period 1 and Period 2 (Per1, Per2) and has been shown to reorganize by relative day lengths (Inagaki et al., 2007). However, it is not yet clearly understood what underlies the spatial patterning of Per1 and Per2 expression (Yamaguchi et al., 2003; Foley et al., 2011) and its plasticity. We found that the period of the oscillation in Bmal1 expression, a positive-feedback component of the circadian clock, preserves the behavioral circadian period under culture and drives clustered oscillations in the mouse SCN. Pharmacological and physical isolations of SCN subregions indicate that the period of Bmal1 oscillation is subregion specific and is preserved during culture. Together with computer simulations, we show that either the intercellular coupling does not strongly influence the Bmal1 oscillation or the nature of the coupling is more complex than previously assumed. Furthermore, we have found that the region-specific periods are modulated by the light conditions that an animal is exposed to. Based on these, we suggest that the period forms the basis of seasonal coding in the SCN. © 2012 the authors.

AB - Circadian oscillators in the suprachiasmatic nucleus (SCN) collectively orchestrate 24 h rhythms in the body while also coding for seasonal rhythms. Although synchronization is required among SCN oscillators to provide robustness for regular timekeeping (Herzog et al., 2004), heterogeneity of period and phase distributions is needed to accommodate seasonal variations in light duration (Pittendrigh and Daan, 1976b). In the mouse SCN, the heterogeneous phase distribution has been recently found in the cycling of clock genes Period 1 and Period 2 (Per1, Per2) and has been shown to reorganize by relative day lengths (Inagaki et al., 2007). However, it is not yet clearly understood what underlies the spatial patterning of Per1 and Per2 expression (Yamaguchi et al., 2003; Foley et al., 2011) and its plasticity. We found that the period of the oscillation in Bmal1 expression, a positive-feedback component of the circadian clock, preserves the behavioral circadian period under culture and drives clustered oscillations in the mouse SCN. Pharmacological and physical isolations of SCN subregions indicate that the period of Bmal1 oscillation is subregion specific and is preserved during culture. Together with computer simulations, we show that either the intercellular coupling does not strongly influence the Bmal1 oscillation or the nature of the coupling is more complex than previously assumed. Furthermore, we have found that the region-specific periods are modulated by the light conditions that an animal is exposed to. Based on these, we suggest that the period forms the basis of seasonal coding in the SCN. © 2012 the authors.

KW - PER2 protein

KW - protein BMAL1

KW - animal experiment

KW - animal tissue

KW - article

KW - bioluminescence

KW - circadian rhythm

KW - computer simulation

KW - female

KW - immunofluorescence

KW - immunohistochemistry

KW - light dark cycle

KW - locomotion

KW - male

KW - mouse

KW - nonbiological model

KW - nonhuman

KW - plasticity

KW - priority journal

KW - protein expression

KW - suprachiasmatic nucleus

KW - transgenic mouse

KW - Action Potentials

KW - Animals

KW - ARNTL Transcription Factors

KW - Biological Clocks

KW - Brain Mapping

KW - Circadian Rhythm

KW - Cluster Analysis

KW - GABA Antagonists

KW - Gene Expression Regulation

KW - Luminescent Proteins

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Models, Neurological

KW - Motor Activity

KW - Neurons

KW - Nonlinear Dynamics

KW - Organ Culture Techniques

KW - Period Circadian Proteins

KW - Photoperiod

KW - Pyridazines

KW - Sodium Channel Blockers

KW - Software

KW - Statistics as Topic

KW - Suprachiasmatic Nucleus

KW - Tetrodotoxin

U2 - 10.1523/JNEUROSCI.5586-11.2012

DO - 10.1523/JNEUROSCI.5586-11.2012

M3 - Article

VL - 32

SP - 8900

EP - 8918

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 26

ER -