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Individual cellular clocks in the suprachiasmatic nucleus (SCN),the circadian center, are integrated into a stable and robustpacemaker with a period length of about 24 hours. We used real-timeanalysis of gene expression to show synchronized rhythms ofclock gene transcription across hundreds of neurons within themammalian SCN in organotypic slice culture. Differentially phasedneuronal clocks are topographically arranged across the SCN.A protein synthesis inhibitor set all cell clocks to the sameinitial phase and, after withdrawal, intrinsic interactionsamong cell clocks reestablished the stable program of gene expressionacross the assemblage. Na+-dependent action potentials contributedto establishing cellular synchrony and maintaining spontaneousoscillation across the SCN.
1 Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. 2 Department of Physics, Informatics, and Biology, Yamaguchi University, Yamaguchi 753-8512, Japan. 3 Department of Electronics, Tohoku Institute of Technology, Sendai 982-8577, Japan.
* To whom correspondence should be addressed. E-mail: okamurah{at}kobe-u.ac.jp
Ryanodine-Sensitive Intracellular Ca2+ Channels in Rat Suprachiasmatic Nuclei Are Required for Circadian Clock Control of Behavior.
C. Mercado, M. Diaz-Munoz, J. Alamilla, K. Valderrama, V. Morales-Tlalpan, and R. Aguilar-Roblero (2009)
J Biol Rhythms
24, 203-210
|Abstract »|PDF »
Small-World Network Models of Intercellular Coupling Predict Enhanced Synchronization in the Suprachiasmatic Nucleus.
C. Vasalou, E. D. Herzog, and M. A. Henson (2009)
J Biol Rhythms
24, 243-254
|Abstract »|PDF »
The Neuropeptide Pigment-Dispersing Factor Adjusts Period and Phase of Drosophila's Clock.
T. Yoshii, C. Wulbeck, H. Sehadova, S. Veleri, D. Bichler, R. Stanewsky, and C. Helfrich-Forster (2009)
J. Neurosci.
29, 2597-2610
|Abstract »|Full Text »|PDF »
Spatiotemporal Heterogeneity in the Electrical Activity of Suprachiasmatic Nuclei Neurons and their Response to Photoperiod.
T.M. Brown and H.D. Piggins (2009)
J Biol Rhythms
24, 44-54
|Abstract »|PDF »
Increased Coherence of Circadian Rhythms in Mature Fibroblast Cultures.
J. S. O'Neill and M. H. Hastings (2008)
J Biol Rhythms
23, 483-488
|Abstract »|PDF »
A genetic timer through noise-induced stabilization of an unstable state.
M. Turcotte, J. Garcia-Ojalvo, and G. M. Suel (2008)
PNAS
105, 15732-15737
|Abstract »|Full Text »|PDF »
Decline of the Presynaptic Network, Including GABAergic Terminals, in the Aging Suprachiasmatic Nucleus of the Mouse.
M. Palomba, M. Nygard, F. Florenzano, G. Bertini, K. Kristensson, and M. Bentivoglio (2008)
J Biol Rhythms
23, 220-231
|Abstract »|PDF »
cAMP-Dependent Signaling as a Core Component of the Mammalian Circadian Pacemaker.
J. S. O'Neill, E. S. Maywood, J. E. Chesham, J. S. Takahashi, and M. H. Hastings (2008)
Science
320, 949-953
|Abstract »|Full Text »|PDF »
Mitogen-Activated Protein Kinase Is a Functional Component of the Autonomous Circadian System in the Suprachiasmatic Nucleus.
M. Akashi, N. Hayasaka, S. Yamazaki, and K. Node (2008)
J. Neurosci.
28, 4619-4623
|Abstract »|Full Text »|PDF »
Interferon-{gamma} Alters Electrical Activity and Clock Gene Expression in Suprachiasmatic Nucleus Neurons.
Y. Kwak, G. B. Lundkvist, J. Brask, A. Davidson, M. Menaker, K. Kristensson, and G. D. Block (2008)
J Biol Rhythms
23, 150-159
|Abstract »|PDF »
Circadian Behavioral Rhythms in Cry1/Cry2 Double-Deficient Mice Induced by Methamphetamine.
S. Honma, T. Yasuda, A. Yasui, G. T. J. van der Horst, and K.-i. Honma (2008)
J Biol Rhythms
23, 91-94
|PDF »
Metabolic rhythm abnormalities in mice lacking VIP-VPAC2 signaling.
D. A. Bechtold, T. M. Brown, S. M. Luckman, and H. D. Piggins (2008)
Am J Physiol Regulatory Integrative Comp Physiol
294, R344-R351
|Abstract »|Full Text »|PDF »
Pigment Dispersing Factor-Dependent and -Independent Circadian Locomotor Behavioral Rhythms.
V. Sheeba, V. K. Sharma, H. Gu, Y.-T. Chou, D. K. O'Dowd, and T. C. Holmes (2008)
J. Neurosci.
28, 217-227
|Abstract »|Full Text »|PDF »
Computational Analysis of Mammalian Cell Division Gated by a Circadian Clock: Quantized Cell Cycles and Cell Size Control.
J. Zamborszky, C. I. Hong, and A. Csikasz Nagy (2007)
J Biol Rhythms
22, 542-553
|Abstract »|PDF »
Minireview: The Circadian Clockwork of the Suprachiasmatic Nuclei Analysis of a Cellular Oscillator that Drives Endocrine Rhythms.
E. S. Maywood, J. S. O'Neill, J. E. Chesham, and M. H. Hastings (2007)
Endocrinology
148, 5624-5634
|Abstract »|Full Text »|PDF »
Minireview: The Neuroendocrinology of the Suprachiasmatic Nucleus as a Conductor of Body Time in Mammals.
Intracellular Ca2+ Regulates Free-Running Circadian Clock Oscillation In Vivo.
M. C. Harrisingh, Y. Wu, G. A. Lnenicka, and M. N. Nitabach (2007)
J. Neurosci.
27, 12489-12499
|Abstract »|Full Text »|PDF »
Circadian clocks: regulators of endocrine and metabolic rhythms.
M. Hastings, J. S O'Neill, and E. S Maywood (2007)
J. Endocrinol.
195, 187-198
|Abstract »|Full Text »|PDF »
A Role for Androgens in Regulating Circadian Behavior and the Suprachiasmatic Nucleus.
I. N. Karatsoreos, A. Wang, J. Sasanian, and R. Silver (2007)
Endocrinology
148, 5487-5495
|Abstract »|Full Text »|PDF »
Modeling the Electrophysiology of Suprachiasmatic Nucleus Neurons.
Choon Kiat Sim and D. B. Forger (2007)
J Biol Rhythms
22, 445-453
|Abstract »|PDF »
Beyond Intuitive Modeling: Combining Biophysical Models with Innovative Experiments to Move the Circadian Clock Field Forward.
D. Forger, D. Gonze, D. Virshup, and D. K. Welsh (2007)
J Biol Rhythms
22, 200-210
|Abstract »|PDF »
Modeling the Behavior of Coupled Cellular Circadian Oscillators in the Suprachiasmatic Nucleus.
P. Indic, W. J. Schwartz, E. D. Herzog, N. C. Foley, and M. C. Antle (2007)
J Biol Rhythms
22, 211-219
|Abstract »|PDF »
Dynamics of the Adjustment of Clock Gene Expression in the Rat Suprachiasmatic Nucleus to an Asymmetrical Change from a Long to a Short Photoperiod.
A. Sumova, Z. Kovacikova, and H. Illnerova (2007)
J Biol Rhythms
22, 259-267
|Abstract »|PDF »
The After-Hours Mutant Reveals a Role for Fbxl3 in Determining Mammalian Circadian Period.
S. I. H. Godinho, E. S. Maywood, L. Shaw, V. Tucci, A. R. Barnard, L. Busino, M. Pagano, R. Kendall, M. M. Quwailid, M. R. Romero, et al. (2007)
Science
316, 897-900
|Abstract »|Full Text »|PDF »
Circadian desynchronization of core body temperature and sleep stages in the rat.
T. Cambras, J. R. Weller, M. Angles-Pujoras, M. L. Lee, A. Christopher, A. Diez-Noguera, J. M. Krueger, and H. O. de la Iglesia (2007)
PNAS
104, 7634-7639
|Abstract »|Full Text »|PDF »
Separate oscillating cell groups in mouse suprachiasmatic nucleus couple photoperiodically to the onset and end of daily activity.
N. Inagaki, S. Honma, D. Ono, Y. Tanahashi, and K.-i. Honma (2007)
PNAS
104, 7664-7669
|Abstract »|Full Text »|PDF »
Disrupted Neuronal Activity Rhythms in the Suprachiasmatic Nuclei of Vasoactive Intestinal Polypeptide-Deficient Mice.
T. M. Brown, C. S. Colwell, J. A. Waschek, and H. D. Piggins (2007)
J Neurophysiol
97, 2553-2558
|Abstract »|Full Text »|PDF »
Circadian and CLOCK-controlled regulation of the mouse transcriptome and cell proliferation.
B. H. Miller, E. L. McDearmon, S. Panda, K. R. Hayes, J. Zhang, J. L. Andrews, M. P. Antoch, J. R. Walker, K. A. Esser, J. B. Hogenesch, et al. (2007)
PNAS
104, 3342-3347
|Abstract »|Full Text »|PDF »
Synchronizing multiphasic circadian rhythms of rhodopsin promoter expression in rod photoreceptor cells.
Gates and Oscillators II: Zeitgebers and the Network Model of the Brain Clock.
M. C. Antle, N. C. Foley, D. K. Foley, and R. Silver (2007)
J Biol Rhythms
22, 14-25
|Abstract »|PDF »
Gate Cells See the Light.
D. K. Welsh (2007)
J Biol Rhythms
22, 26-28
|PDF »
Bimodal Clock Gene Expression in Mouse Suprachiasmatic Nucleus and Peripheral Tissues Under a 7-Hour Light and 5-Hour Dark Schedule.
T. Watanabe, E. Naito, N. Nakao, H. Tei, T. Yoshimura, and S. Ebihara (2007)
J Biol Rhythms
22, 58-68
|Abstract »|PDF »
Prokineticin receptor 2 (Prokr2) is essential for the regulation of circadian behavior by the suprachiasmatic nuclei.
H. M. Prosser, A. Bradley, J. E. Chesham, F. J. P. Ebling, M. H. Hastings, and E. S. Maywood (2007)
PNAS
104, 648-653
|Abstract »|Full Text »|PDF »
Depolarization and Neurotransmitter Regulation of Vasopressin Gene Expression in the Rat Suprachiasmatic Nucleus In Vitro.
M. Rusnak, Z. E. Toth, S. B. House, and H. Gainer (2007)
J. Neurosci.
27, 141-151
|Abstract »|Full Text »|PDF »
Biological Rhythms Workshop IB: Neurophysiology of SCN Pacemaker Function.
S. J. Kuhlman (2007)
Cold Spring Harb Symp Quant Biol
72, 21-33
|Abstract »|PDF »
Genetic and Molecular Analysis of the Central and Peripheral Circadian Clockwork of Mice.
E. S. Maywood, J. S. O'Neill, A. B. Reddy, J. E. Chesham, H. M. Prosser, C. P. Kyriacou, S. I. H. Godinho, P. M. Nolan, and M. H. Hastings (2007)
Cold Spring Harb Symp Quant Biol
72, 85-94
|Abstract »|PDF »
Peripheral Clocks: Keeping Up with the Master Clock.
E. Kowalska and S. A. Brown (2007)
Cold Spring Harb Symp Quant Biol
72, 301-305
|Abstract »|PDF »
Stochastic Phase Oscillators and Circadian Bioluminescence Recordings.
J. Rougemont and F. Naef (2007)
Cold Spring Harb Symp Quant Biol
72, 405-411
|Abstract »|PDF »
Exploring Spatiotemporal Organization of SCN Circuits.
L. Yan, I. Karatsoreos, J. LeSauter, D. K. Welsh, S. Kay, D. Foley, and R. Silver (2007)
Cold Spring Harb Symp Quant Biol
72, 527-541
|Abstract »|PDF »
Suprachiasmatic Nucleus Clock Time in the Mammalian Circadian System.
H. Okamura (2007)
Cold Spring Harb Symp Quant Biol
72, 551-556
|Abstract »|PDF »
GABA and Gi/o differentially control circadian rhythms and synchrony in clock neurons.
S. J. Aton, J. E. Huettner, M. Straume, and E. D. Herzog (2006)
PNAS
103, 19188-19193
|Abstract »|Full Text »|PDF »
Encoding the Ins and Outs of Circadian Pacemaking.
S. J. Kuhlman and D. G. McMahon (2006)
J Biol Rhythms
21, 470-481
|Abstract »|PDF »
Systems Biology of Circadian Rhythms: An Outlook.
L. De Haro and S. Panda (2006)
J Biol Rhythms
21, 507-518
|Abstract »|PDF »
Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS).
K. Vanselow, J. T. Vanselow, P. O. Westermark, S. Reischl, B. Maier, T. Korte, A. Herrmann, H. Herzel, A. Schlosser, and A. Kramer (2006)
Genes & Dev.
20, 2660-2672
|Abstract »|Full Text »|PDF »
Circadian intraocular pressure rhythm is generated by clock genes..
A. Maeda, S. Tsujiya, T. Higashide, K. Toida, T. Todo, T. Ueyama, H. Okamura, and K. Sugiyama (2006)
Invest. Ophthalmol. Vis. Sci.
47, 4050-4052
|Abstract »|Full Text »|PDF »
Simulation of Day-Length Encoding in the SCN: From Single-Cell to Tissue-Level Organization.
J. Rohling, L. Wolters, and J. H. Meijer (2006)
J Biol Rhythms
21, 301-313
|Abstract »|PDF »
Two Circadian Timing Circuits in Neurospora crassa Cells Share Components and Regulate Distinct Rhythmic Processes.
R. M. de Paula, Z. A. Lewis, A. V. Greene, K. S. Seo, L. W. Morgan, M. W. Vitalini, L. Bennett, R. H. Gomer, and D. Bell-Pedersen (2006)
J Biol Rhythms
21, 159-168
|Abstract »|PDF »
Phase Angle Difference Alters Coupling Relations of Functionally Distinct Circadian Oscillators Revealed by Rhythm Splitting.
M. R. Gorman and N. A. Steele (2006)
J Biol Rhythms
21, 195-205
|Abstract »|PDF »
Chronic Treatment with Prednisolone Represses the Circadian Oscillation of Clock Gene Expression in Mouse Peripheral Tissues.
S. Koyanagi, S. Okazawa, Y. Kuramoto, K. Ushijima, H. Shimeno, S. Soeda, H. Okamura, and S. Ohdo (2006)
Mol. Endocrinol.
20, 573-583
|Abstract »|Full Text »|PDF »
History-Dependent Changes in Entrainment of the Activity Rhythm in the Syrian Hamster (Mesocricetus auratus).
J. J. Chiesa, M. Angles-Pujolras, A. Diez-Noguera, and T. Cambras (2006)
J Biol Rhythms
21, 45-57
|Abstract »|PDF »
Real-time imaging of the somite segmentation clock: Revelation of unstable oscillators in the individual presomitic mesoderm cells.
Y. Masamizu, T. Ohtsuka, Y. Takashima, H. Nagahara, Y. Takenaka, K. Yoshikawa, H. Okamura, and R. Kageyama (2006)
PNAS
103, 1313-1318
|Abstract »|Full Text »|PDF »
Electrical Hyperexcitation of Lateral Ventral Pacemaker Neurons Desynchronizes Downstream Circadian Oscillators in the Fly Circadian Circuit and Induces Multiple Behavioral Periods.
M. N. Nitabach, Y. Wu, V. Sheeba, W. C. Lemon, J. Strumbos, P. K. Zelensky, B. H. White, and T. C. Holmes (2006)
J. Neurosci.
26, 479-489
|Abstract »|Full Text »|PDF »
Gastrin-Releasing Peptide Promotes Suprachiasmatic Nuclei Cellular Rhythmicity in the Absence of Vasoactive Intestinal Polypeptide-VPAC2 Receptor Signaling.
T. M. Brown, A. T. Hughes, and H. D. Piggins (2005)
J. Neurosci.
25, 11155-11164
|Abstract »|Full Text »|PDF »
c-Fos Expression in the Brains of Behaviorally "Split" Hamsters in Constant Light: Calling Attention to a Dorsolateral Region of the Suprachiasmatic Nucleus and the Medial Division of the Lateral Habenula.
M. Tavakoli-Nezhad and W. J. Schwartz (2005)
J Biol Rhythms
20, 419-429
|Abstract »|PDF »
Activity rhythm of golden hamster (Mesocricetus auratus) can be entrained to a 19-h light-dark cycle.
J. J. Chiesa, M. Angles-Pujolras, A. Diez-Noguera, and T. Cambras (2005)
Am J Physiol Regulatory Integrative Comp Physiol
289, R998-R1005
|Abstract »|Full Text »|PDF »
Two Antiphase Oscillations Occur in Each Suprachiasmatic Nucleus of Behaviorally Split Hamsters.
L. Yan, N. C. Foley, J. M. Bobula, L. J. Kriegsfeld, and R. Silver (2005)
J. Neurosci.
25, 9017-9026
|Abstract »|Full Text »|PDF »
A Calcium Flux Is Required for Circadian Rhythm Generation in Mammalian Pacemaker Neurons.
G. B. Lundkvist, Y. Kwak, E. K. Davis, H. Tei, and G. D. Block (2005)
J. Neurosci.
25, 7682-7686
|Abstract »|Full Text »|PDF »
Differential Response of Period 1 Expression within the Suprachiasmatic Nucleus.
W. Nakamura, S. Yamazaki, N. N. Takasu, K. Mishima, and G. D. Block (2005)
J. Neurosci.
25, 5481-5487
|Abstract »|Full Text »|PDF »
Entrainment in a Model of the Mammalian Circadian Oscillator.
F. Geier, S. Becker-Weimann, A. Kramer, and H. Herzel (2005)
J Biol Rhythms
20, 83-93
|Abstract »|PDF »
Circadian Rhythm Generation and Entrainment in Astrocytes.
L. M. Prolo, J. S. Takahashi, and E. D. Herzog (2005)
J. Neurosci.
25, 404-408
|Abstract »|Full Text »|PDF »
Stochastic simulation of the mammalian circadian clock.
