Cell autonomy and synchrony of suprachiasmatic nucleus circadian oscillators

The suprachiasmatic nucleus (SCN) of the hypothalamus is the site of the master circadian pacemaker in mammals. The individual cells of the SCN are capable of functioning independently from one another and therefore must form a cohesive circadian network through intercellular coupling. The network properties of the SCN lead to coordination of circadian rhythms among its neurons and neuronal subpopulations. There is increasing evidence for multiple interconnected oscillators within the SCN, and in this review we will highlight recent advances in our knowledge of the complex organization and function of the cellular and network-level SCN clock. Understanding the way in which synchrony is achieved between cells in the SCN will provide insight into the means by which this important nucleus orchestrates circadian rhythms throughout the organism.

[1]  H. Heller,et al.  Circadian Rhythms in the Suprachiasmatic Nucleus are Temperature-Compensated and Phase-Shifted by Heat Pulses In Vitro , 1999, The Journal of Neuroscience.

[2]  Alexis B. Webb,et al.  Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons , 2009, Proceedings of the National Academy of Sciences.

[3]  Ying Xu,et al.  Functional consequences of a CKIδ mutation causing familial advanced sleep phase syndrome , 2005, Nature.

[4]  Richard W Aldrich,et al.  BK calcium-activated potassium channels regulate circadian behavioral rhythms and pacemaker output , 2006, Nature Neuroscience.

[5]  B. Rusak,et al.  Neuropeptides phase shift the mammalian circadian pacemaker , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  J. Hannibal,et al.  Vasoactive intestinal polypeptide induces per1 and per2 gene expression in the rat suprachiasmatic nucleus late at night , 2002, The European journal of neuroscience.

[7]  J. Takahashi,et al.  cAMP-Dependent Signaling as a Core Component of the Mammalian Circadian Pacemaker , 2008, Science.

[8]  Francis J. Doyle,et al.  Intercellular Coupling Confers Robustness against Mutations in the SCN Circadian Clock Network , 2007, Cell.

[9]  Anthony J. Harmar,et al.  Synchronization and Maintenance of Timekeeping in Suprachiasmatic Circadian Clock Cells by Neuropeptidergic Signaling , 2006, Current Biology.

[10]  Shin Yamazaki,et al.  Constant light desynchronizes mammalian clock neurons , 2005, Nature Neuroscience.

[11]  M. Vansteensel,et al.  Seasonal Encoding by the Circadian Pacemaker of the SCN , 2007, Current Biology.

[12]  Daniel B. Forger,et al.  Emergence of Noise-Induced Oscillations in the Central Circadian Pacemaker , 2010, PLoS biology.

[13]  J. Vanecek,et al.  In vitro entrainment of the circadian rhythm of vasopressin-releasing cells in suprachiasmatic nucleus by vasoactive intestinal polypeptide , 2000, Brain Research.

[14]  L. P. Morin,et al.  Complex organization of mouse and rat suprachiasmatic nucleus , 2006, Neuroscience.

[15]  H. Underwood,et al.  Pineal Melatonin Rhythms in the Lizard Anolis carolinensis: I. Response to Light and Temperature Cycles , 1987, Journal of biological rhythms.

[16]  Boyoung Lee,et al.  CREB Influences Timing and Entrainment of the SCN Circadian Clock , 2010, Journal of biological rhythms.

[17]  Achim Kramer,et al.  Synchronization-Induced Rhythmicity of Circadian Oscillators in the Suprachiasmatic Nucleus , 2007, PLoS Comput. Biol..

[18]  J. Harper,et al.  SCFβ-TRCP Controls Clock-dependent Transcription via Casein Kinase 1-dependent Degradation of the Mammalian Period-1 (Per1) Proteinm* , 2005, Journal of Biological Chemistry.

[19]  W J Schwartz,et al.  Antiphase oscillation of the left and right suprachiasmatic nuclei. , 2000, Science.

[20]  J. Takahashi,et al.  Inducible and Reversible Clock Gene Expression in Brain Using the tTA System for the Study of Circadian Behavior , 2007, PLoS genetics.

[21]  Steven M Reppert,et al.  GABA Synchronizes Clock Cells within the Suprachiasmatic Circadian Clock , 2000, Neuron.

[22]  Erik D Herzog,et al.  Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons , 2005, Nature Neuroscience.

[23]  R. Silver,et al.  Temporal and spatial expression patterns of canonical clock genes and clock‐controlled genes in the suprachiasmatic nucleus , 2004, The European journal of neuroscience.

[24]  K. Mori,et al.  Identification of neuromedin S and its possible role in the mammalian circadian oscillator system , 2005, The EMBO journal.

[25]  William J Schwartz,et al.  Forced Desynchronization of Dual Circadian Oscillators within the Rat Suprachiasmatic Nucleus , 2004, Current Biology.

[26]  Johanna H. Meijer,et al.  Heterogeneity of rhythmic suprachiasmatic nucleus neurons: Implications for circadian waveform and photoperiodic encoding , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[27]  David K Welsh,et al.  Suprachiasmatic nucleus: cell autonomy and network properties. , 2010, Annual review of physiology.

[28]  M. Menaker,et al.  Temporal chimeras produced by hypothalamic transplants , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  Peter G. Schultz,et al.  High-Throughput Chemical Screen Identifies a Novel Potent Modulator of Cellular Circadian Rhythms and Reveals CKIα as a Clock Regulatory Kinase , 2010, PLoS biology.

[30]  Population Encoding by Circadian Clock Neurons Organizes Circadian Behavior , 2009, The Journal of Neuroscience.

[31]  R. Moore,et al.  Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. , 1972, Brain research.

[32]  J. Takahashi,et al.  Mammalian circadian biology: elucidating genome-wide levels of temporal organization. , 2004, Annual review of genomics and human genetics.

[33]  S. Daan,et al.  Influence of photoperiod duration and light–dark transitions on entrainment of Per1 and Per2 gene and protein expression in subdivisions of the mouse suprachiasmatic nucleus , 2009, The European journal of neuroscience.

[34]  Daisuke Ono,et al.  Separate oscillating cell groups in mouse suprachiasmatic nucleus couple photoperiodically to the onset and end of daily activity , 2007, Proceedings of the National Academy of Sciences.

[35]  W. O. Friesen,et al.  Dissociation of circadian and light inhibition of melatonin release through forced desynchronization in the rat , 2009, Proceedings of the National Academy of Sciences.

[36]  Joseph S. Takahashi,et al.  Chimera Analysis of the Clock Mutation in Mice Shows that Complex Cellular Integration Determines Circadian Behavior , 2001, Cell.

[37]  M. Pagano,et al.  The After-Hours Mutant Reveals a Role for Fbxl3 in Determining Mammalian Circadian Period , 2007, Science.

[38]  Wataru Nakamura,et al.  Differential Response of Period 1 Expression within the Suprachiasmatic Nucleus , 2005, The Journal of Neuroscience.

[39]  R. Moore,et al.  The suprachiasmatic nucleus of the golden hamster: Immunohistochemical analysis of cell and fiber distribution , 1984, Neuroscience.

[40]  H. O. de la Iglesia,et al.  Circadian desynchronization of core body temperature and sleep stages in the rat , 2007, Proceedings of the National Academy of Sciences.

[41]  C. Colwell,et al.  Disrupted neuronal activity rhythms in the suprachiasmatic nuclei of vasoactive intestinal polypeptide-deficient mice. , 2007, Journal of neurophysiology.

[42]  L. P. Morin,et al.  SCN Organization Reconsidered , 2007, Journal of biological rhythms.

[43]  C. Allen,et al.  Neuropeptide‐mediated calcium signaling in the suprachiasmatic nucleus network , 2010, The European journal of neuroscience.

[44]  H. Tokura,et al.  Effects of temperature on the circadian rhythm of pig-tailed macaques Macaca nemestrina. , 1983, The American journal of physiology.

[45]  S. Honma,et al.  Two distinct oscillators in the rat suprachiasmatic nucleus in vitro. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[46]  S. Honma,et al.  Clock mutation lengthens the circadian period without damping rhythms in individual SCN neurons , 2002, Nature Neuroscience.

[47]  A. Meredith,et al.  BK Channels Regulate Spontaneous Action Potential Rhythmicity in the Suprachiasmatic Nucleus , 2008, PloS one.

[48]  D. Cutler,et al.  Aberrant Gating of Photic Input to the Suprachiasmatic Circadian Pacemaker of Mice Lacking the VPAC2 Receptor , 2004, Journal of Neuroscience.

[49]  K. Mori,et al.  Identification and functional analysis of a novel ligand for G protein-coupled receptor, Neuromedin S , 2008, Regulatory Peptides.

[50]  Erik D Herzog,et al.  Vasoactive intestinal polypeptide requires parallel changes in adenylate cyclase and phospholipase C to entrain circadian rhythms to a predictable phase. , 2011, Journal of neurophysiology.

[51]  B. Swanson,et al.  Circadian Timing of REM Sleep Is Coupled to an Oscillator within the Dorsomedial Suprachiasmatic Nucleus , 2009, Current Biology.

[52]  J. Redman,et al.  Entrainment of Activity Rhythms to Temperature Cycles in Diurnal Palm Squirrels , 1998, Physiology & Behavior.

[53]  C. Pittendrigh,et al.  Circadian rhythms and the circadian organization of living systems. , 1960, Cold Spring Harbor symposia on quantitative biology.

[54]  Yoshiyuki Sakaki,et al.  Temporal Precision in the Mammalian Circadian System: A Reliable Clock from Less Reliable Neurons , 2004, Journal of biological rhythms.

[55]  D. Bechtold,et al.  Setting Clock Speed in Mammals: The CK1ɛ tau Mutation in Mice Accelerates Circadian Pacemakers by Selectively Destabilizing PERIOD Proteins , 2008, Neuron.

[56]  Y Sakaki,et al.  Resetting central and peripheral circadian oscillators in transgenic rats. , 2000, Science.

[57]  S. Yamaguchi,et al.  Synchronization of Cellular Clocks in the Suprachiasmatic Nucleus , 2003, Science.

[58]  Shizufumi Ebihara,et al.  Reorganization of the Suprachiasmatic Nucleus Coding for Day Length , 2008, Journal of biological rhythms.

[59]  D. Welsh,et al.  Exploring spatiotemporal organization of SCN circuits. , 2007, Cold Spring Harbor symposia on quantitative biology.

[60]  S. Shibata,et al.  Constant light housing attenuates circadian rhythms of mPer2 mRNA AND mPER2 protein expression in the suprachiasmatic nucleus of mice , 2003, Neuroscience.

[61]  Erik D Herzog,et al.  GABA and Gi/o differentially control circadian rhythms and synchrony in clock neurons , 2006, Proceedings of the National Academy of Sciences.

[62]  C. Colwell,et al.  Vasoactive intestinal peptide and the mammalian circadian system. , 2007, General and comparative endocrinology.

[63]  H. Piggins,et al.  Spatiotemporal Heterogeneity in the Electrical Activity of Suprachiasmatic Nuclei Neurons and their Response to Photoperiod , 2009, Journal of biological rhythms.

[64]  H. Herzel,et al.  Coupling governs entrainment range of circadian clocks. Mol Syst Biol 6:438 , 2010 .

[65]  D. Earnest,et al.  Circadian rhythms of vasopressin release from individual rat suprachiasmatic explants in vitro , 1986, Brain Research.

[66]  Yasufumi Shigeyoshi,et al.  An Abrupt Shift in the Day/Night Cycle Causes Desynchrony in the Mammalian Circadian Center , 2003, The Journal of Neuroscience.

[67]  J. Aschoff,et al.  Exogenous and endogenous components in circadian rhythms. , 1960, Cold Spring Harbor symposia on quantitative biology.

[68]  Daniel B. Forger,et al.  An opposite role for tau in circadian rhythms revealed by mathematical modeling. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[69]  R. Mason.  The effects of continuous light exposure on Syrian hamster suprachiasmatic (SCN) neuronal discharge activity in vitro , 1991, Neuroscience Letters.

[70]  Y. Yamada,et al.  Multiscale complexity in the mammalian circadian clock. , 2010, Current opinion in genetics & development.

[71]  Sato Honma,et al.  Circadian periods of single suprachiasmatic neurons in rats , 1998, Neuroscience Letters.

[72]  E. Maywood,et al.  The VPAC2 Receptor Is Essential for Circadian Function in the Mouse Suprachiasmatic Nuclei , 2002, Cell.

[73]  Markus Meister,et al.  Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms , 1995, Neuron.

[74]  R. Moore,et al.  Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections , 2001, Brain Research.

[75]  M. D. Schwartz,et al.  Phase Misalignment between Suprachiasmatic Neuronal Oscillators Impairs Photic Behavioral Phase Shifts But Not Photic Induction of Gene Expression , 2010, The Journal of Neuroscience.

[76]  Joseph S. Takahashi,et al.  Circadian Mutant Overtime Reveals F-box Protein FBXL3 Regulation of Cryptochrome and Period Gene Expression , 2007, Cell.

[77]  M. Gillette,et al.  Response Element-binding Protein ( CREB )-dependent Activation of Per 1 Is Required for Light-induced Signaling in the Suprachiasmatic Nucleus Circadian Clock , 2002 .

[78]  I. Zucker,et al.  Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[79]  T. Kondo,et al.  Nonparametric entrainment of the in vitro circadian phosphorylation rhythm of cyanobacterial KaiC by temperature cycle , 2009, Proceedings of the National Academy of Sciences.

[80]  R. Refinetti.  Entrainment of Circadian Rhythm by Ambient Temperature Cycles in Mice , 2010, Journal of biological rhythms.

[81]  H. Albers,et al.  Analysis of the phase shifting effects of gastrin releasing peptide when microinjected into the suprachiasmatic region , 1995, Neuroscience Letters.

[82]  E. Maywood,et al.  Minireview: The circadian clockwork of the suprachiasmatic nuclei--analysis of a cellular oscillator that drives endocrine rhythms. , 2007, Endocrinology.

[83]  Anne-Marie Chang,et al.  The mouse Clock mutation reduces circadian pacemaker amplitude and enhances efficacy of resetting stimuli and phase-response curve amplitude. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[84]  J. Takahashi,et al.  Molecular components of the mammalian circadian clock. , 2006, Human molecular genetics.

[85]  H. Okamura,et al.  Gradients in the circadian expression of Per1 and Per2 genes in the rat suprachiasmatic nucleus , 2002, The European journal of neuroscience.

[86]  G. Coleman,et al.  The effect of ambient temperature cycles upon circadian running and drinking activity in male and female laboratory rats , 1988, Physiology & Behavior.

[87]  Ook Joon Yoo,et al.  PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[88]  F. Turek,et al.  Central administration of muscimol phase-shifts the mammalian circadian clock , 1989, Journal of Comparative Physiology A.

[89]  Nicholas C. Foley,et al.  Characterization of orderly spatiotemporal patterns of clock gene activation in mammalian suprachiasmatic nucleus , 2011, The European journal of neuroscience.

[90]  José Agosto,et al.  Coupled oscillators control morning and evening locomotor behaviour of Drosophila , 2004, Nature.

[91]  Joseph S. Takahashi,et al.  Temperature as a Universal Resetting Cue for Mammalian Circadian Oscillators , 2010, Science.

[92]  R. Leak,et al.  Suprachiasmatic pacemaker organization analyzed by viral transynaptic transport , 1999, Brain Research.

[93]  Moore Ry.  Organization and function of a central nervous system circadian oscillator: the suprachiasmatic hypothalamic nucleus. , 1983 .

[94]  Steven A. Brown,et al.  Rhythms of Mammalian Body Temperature Can Sustain Peripheral Circadian Clocks , 2002, Current Biology.

[95]  H. Piggins,et al.  Live imaging of altered period1 expression in the suprachiasmatic nuclei of Vipr2−/− mice1 , 2008, Journal of neurochemistry.

[96]  M. A. Rea.  VIP-stimulated cyclic AMP accumulation in the suprachiasmatic hypothalamus , 1990, Brain Research Bulletin.

[97]  Michele Pagano,et al.  SCFFbxl3 Controls the Oscillation of the Circadian Clock by Directing the Degradation of Cryptochrome Proteins , 2007, Science.

[98]  Steven H. Strogatz,et al.  Cellular Construction of a Circadian Clock: Period Determination in the Suprachiasmatic Nuclei , 1997, Cell.

[99]  Erik D. Herzog,et al.  Clock controls circadian period in isolated suprachiasmatic nucleus neurons , 1998, Nature Neuroscience.

[100]  Paolo Sassone-Corsi,et al.  Bimodal regulation of mPeriod promoters by CREB-dependent signaling and CLOCK/BMAL1 activity , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[101]  E. Herzog,et al.  Circadian entrainment to temperature, but not light, in the isolated suprachiasmatic nucleus. , 2003, Journal of neurophysiology.

[102]  A. J. McArthur,et al.  Gastrin-Releasing Peptide Phase-Shifts Suprachiasmatic Nuclei Neuronal Rhythms In Vitro , 2000, The Journal of Neuroscience.

[103]  C S Pittendrigh,et al.  Temperature compensation of the circadian oscillation in drosophila pseudoobscura and its entrainment by temperature cycles. , 1968, Journal of insect physiology.

[104]  Christopher R. Jones,et al.  Modeling of a Human Circadian Mutation Yields Insights into Clock Regulation by PER2 , 2007, Cell.

[105]  Anthony J Harmar,et al.  Family-B G-protein-coupled receptors , 2001, Genome Biology.

[106]  A. Davidson,et al.  Intrinsic Regulation of Spatiotemporal Organization within the Suprachiasmatic Nucleus , 2011, PloS one.

[107]  Michael J. Jutras,et al.  Electrical synapses coordinate activity in the suprachiasmatic nucleus , 2005, Nature Neuroscience.

[108]  C. Colwell,et al.  Disrupted circadian rhythms in VIP- and PHI-deficient mice. , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.

[109]  A. Harmar,et al.  Transgenic approach reveals expression of the VPAC2 receptor in phenotypically defined neurons in the mouse suprachiasmatic nucleus and in its efferent target sites , 2004, The European journal of neuroscience.

[110]  Dan Stoleru,et al.  A resetting signal between Drosophila pacemakers synchronizes morning and evening activity , 2005, Nature.

[111]  Serge Daan,et al.  A functional analysis of circadian pacemakers in nocturnal rodents , 1976, Journal of comparative physiology.

[112]  C. Colwell,et al.  Rhythmic coupling among cells in the suprachiasmatic nucleus. , 2000, Journal of neurobiology.

[113]  Peter Woolf,et al.  Control of Mammalian Circadian Rhythm by CKIε-Regulated Proteasome-Mediated PER2 Degradation , 2005, Molecular and Cellular Biology.

[114]  D. Hazlerigg,et al.  Photoperiod differentially regulates gene expression rhythms in the rostral and caudal SCN , 2005, Current Biology.

[115]  M E Greenberg,et al.  Regulation of CREB phosphorylation in the suprachiasmatic nucleus by light and a circadian clock. , 1993, Science.

[116]  Hanspeter Herzel,et al.  Coupling governs entrainment range of circadian clocks , 2010, Molecular systems biology.