The Clock in the Brain: Neurons, Glia, and Networks in Daily Rhythms

  • Emily SlatEmail author
  • G. Mark FreemanJr.Email author
  • Erik D. HerzogEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 217)


The master coordinator of daily schedules in mammals, located in the ventral hypothalamus, is the suprachiasmatic nucleus (SCN). This relatively small population of neurons and glia generates circadian rhythms in physiology and behavior and synchronizes them to local time. Recent advances have begun to define the roles of specific cells and signals (e.g., peptides, amino acids, and purine derivatives) within this network that generate and synchronize daily rhythms. Here we focus on the best-studied signals between neurons and between glia in the mammalian circadian system with an emphasis on time-of-day pharmacology. Where possible, we highlight how commonly used drugs affect the circadian system.




  1. Abraham U, Granada AE, Westermark PO, Heine M, Kramer A, Herzel H (2010) Coupling governs entrainment range of circadian clocks. Mol Syst Biol 6:438PubMedCrossRefGoogle Scholar
  2. Abrahamson EE, Moore RY (2001) Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections. Brain Res 916:172–191PubMedCrossRefGoogle Scholar
  3. Aida R, Moriya T, Araki M, Akiyama M, Wada K, Wada E, Shibata S (2002) Gastrin-releasing peptide mediates photic entrainable signals to dorsal subsets of suprachiasmatic nucleus via induction of Period gene in mice. Mol Pharmacol 61:26–34PubMedCrossRefGoogle Scholar
  4. Albus H, Vansteensel MJ, Michel S, Block GD, Meijer JH (2005) A GABAergic mechanism is necessary for coupling dissociable ventral and dorsal regional oscillators within the circadian clock. Curr Biol 15:886–893PubMedCrossRefGoogle Scholar
  5. An S, Irwin RP, Allen CN, Tsai CA, Herzog ED (2011) Vasoactive intestinal polypeptide requires parallel changes in adenylate cyclase and phospholipase C to entrain circadian rhythms to a predictable phase. J Neurophysiol 105:2289–2296PubMedCrossRefGoogle Scholar
  6. Antle MC, Foley DK, Foley NC, Silver R (2003) Gates and oscillators: a network model of the brain clock. J Biol Rhythms 18:339–350PubMedCrossRefGoogle Scholar
  7. Antle MC, Kriegsfeld LJ, Silver R (2005) Signaling within the master clock of the brain: localized activation of mitogen-activated protein kinase by gastrin-releasing peptide. J Neurosci 25:2447–2454PubMedCrossRefGoogle Scholar
  8. Antle MC, Foley NC, Foley DK, Silver R (2007) Gates and oscillators II: zeitgebers and the network model of the brain clock. J Biol Rhythms 22:14–25PubMedCrossRefGoogle Scholar
  9. Atkins N, Mitchell JW, Romanova EV, Morgan DJ, Cominski TP, Ecker JL, Pintar JE, Sweedler JV, Gillette MU (2010) Circadian integration of glutamatergic signals by little SAAS in novel suprachiasmatic circuits. PLoS One 5:e12612PubMedCrossRefGoogle Scholar
  10. Aton SJ, Huettner JE, Straume M, Herzog ED (2006) GABA and Gi/o differentially control circadian rhythms and synchrony in clock neurons. Proc Natl Acad Sci USA 103:19188–19193PubMedCrossRefGoogle Scholar
  11. Beaulé C, Swanstrom A, Leone MJ, Herzog ED (2009) Circadian modulation of gene expression, but not glutamate uptake, in mouse and rat cortical astrocytes. PLoS One 4:e7476PubMedCrossRefGoogle Scholar
  12. Belenky MA, Smeraski CA, Provencio I, Sollars PJ, Pickard GE (2003) Melanopsin retinal ganglion cells receive bipolar and amacrine cell synapses. J Comp Neurol 460:380–393PubMedCrossRefGoogle Scholar
  13. Belenky MA, Yarom Y, Pickard GE (2007) Heterogeneous expression of gamma-aminobutyric acid and gamma-aminobutyric acid-associated receptors and transporters in the rat suprachiasmatic nucleus. J Comp Neurol 506:708–732CrossRefGoogle Scholar
  14. Bennett MR, Schwartz WJ (1994) Astrocytes in circadian rhythm generation and regulation. Neuroreport 5:1697CrossRefGoogle Scholar
  15. Brown TM, Hughes AT, Piggins HD (2005) Gastrin-releasing peptide promotes suprachiasmatic nuclei cellular rhythmicity in the absence of vasoactive intestinal polypeptide-VPAC2 receptor signaling. J Neurosci 25:11155–11164PubMedCrossRefGoogle Scholar
  16. Brown TM, McLachlan E, Piggins HD (2008) Angiotensin II regulates the activity of mouse suprachiasmatic nuclei neurons. Neuroscience 154:839–847PubMedCrossRefGoogle Scholar
  17. Bryant DN, LeSauter J, Silver R, Romero MT (2000) Retinal innervation of calbindin-D28K cells in the hamster suprachiasmatic nucleus: ultrastructural characterization. J Biol Rhythms 15:103–111PubMedCrossRefGoogle Scholar
  18. Burkeen JF, Womac AD, Earnest DJ, Zoran MJ (2011) Mitochondrial calcium signaling mediates rhythmic extracellular ATP accumulation in suprachiasmatic nucleus astrocytes. J Neurosci 31:8432–8440PubMedCrossRefGoogle Scholar
  19. Burlet A, Marchetti J (1975) Immunoreactive vasopressin in the supra-chiasmatic nucleus. Preliminary data in rats. C R Seances Soc Biol Fil 169:148–151PubMedGoogle Scholar
  20. Cambras T, Weller JR, Anglès-Pujoràs M, Lee ML, Christopher A, Díez-Noguera A, Krueger JM, de la Iglesia HO (2007) Circadian desynchronization of core body temperature and sleep stages in the rat. Proc Natl Acad Sci USA 104:7634–7639PubMedCrossRefGoogle Scholar
  21. Cashion AB, Smith MJ, Wise PM (2003) The morphometry of astrocytes in the rostral preoptic area exhibits a diurnal rhythm on proestrus: relationship to the luteinizing hormone surge and effects of age. Endocrinology 144:274–280PubMedCrossRefGoogle Scholar
  22. Chikahisa S, Séi H (2011) The role of ATP in sleep regulation. Front Neurol 2:87PubMedCrossRefGoogle Scholar
  23. Choi HJ, Lee CJ, Schroeder A, Kim YS, Jung SH, Kim JS, Kim DY, Son EJ, Han HC, Hong SK et al (2008) Excitatory actions of GABA in the suprachiasmatic nucleus. J Neurosci 28:5450–5459PubMedCrossRefGoogle Scholar
  24. de la Iglesia HO, Cambras T, Schwartz WJ, Díez-Noguera A (2004) Forced desynchronization of dual circadian oscillators within the rat suprachiasmatic nucleus. Curr Biol 14:796–800PubMedCrossRefGoogle Scholar
  25. Dickinson PS (2006) Neuromodulation of central pattern generators in invertebrates and vertebrates. Curr Opin Neurobiol 16:604–614PubMedCrossRefGoogle Scholar
  26. Ding JM, Buchanan GF, Tischkau SA, Chen D, Kuriashkina L, Faiman LE, Alster JM, McPherson PS, Campbell KP, Gillette MU (1998) A neuronal ryanodine receptor mediates light-induced phase delays of the circadian clock. Nature 394:381–384PubMedCrossRefGoogle Scholar
  27. Drouyer E, LeSauter J, Hernandez AL, Silver R (2010) Specializations of gastrin-releasing peptide cells of the mouse suprachiasmatic nucleus. J Comp Neurol 518:1249–1263PubMedGoogle Scholar
  28. Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24:31–55PubMedCrossRefGoogle Scholar
  29. Earnest DJ, Sladek CD (1986) Circadian rhythms of vasopressin release from individual rat suprachiasmatic explants in vitro. Brain Res 382:129–133PubMedCrossRefGoogle Scholar
  30. Ehlen JC, Novak CM, Karom MC, Gamble KL, Albers HE (2008) Interactions of GABAA receptor activation and light on period mRNA expression in the suprachiasmatic nucleus. J Biol Rhythms 23:16–25PubMedCrossRefGoogle Scholar
  31. Fields RD, Burnstock G (2006) Purinergic signalling in neuron-glia interactions. Nat Rev Neurosci 7:423–436PubMedCrossRefGoogle Scholar
  32. Francl JM, Kaur G, Glass JD (2010) Regulation of vasoactive intestinal polypeptide release in the suprachiasmatic nucleus circadian clock. Neuroreport 21:1055–1059PubMedCrossRefGoogle Scholar
  33. Francois-Bellan AM, Segu L, Hery M (1989) Regulation by estradiol of GABAA and GABAB binding sites in the diencephalon of the rat: an autoradiographic study. Brain Res 503:144–147PubMedCrossRefGoogle Scholar
  34. Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133PubMedGoogle Scholar
  35. Fricker LD, McKinzie AA, Sun J, Curran E, Qian Y, Yan L, Patterson SD, Courchesne PL, Richards B, Levin N et al (2000) Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing. J Neurosci 20:639–648PubMedGoogle Scholar
  36. Gamble KL, Allen GC, Zhou T, McMahon DG (2007) Gastrin-releasing peptide mediates light-like resetting of the suprachiasmatic nucleus circadian pacemaker through cAMP response element-binding protein and Per1 activation. J Neurosci 27:12078–12087PubMedCrossRefGoogle Scholar
  37. Gannon RL, Cato MJ, Kelley KH, Armstrong DL, Rea MA (1995) GABAergic modulation of optic nerve-evoked field potentials in the rat suprachiasmatic nucleus. Brain Res 694:264–270PubMedCrossRefGoogle Scholar
  38. Gao B, Fritschy JM, Moore RY (1995) GABA A-receptor subunit composition in the circadian timing system. Brain Res 700:142–156PubMedCrossRefGoogle Scholar
  39. Gerhold LM, Wise PM (2006) Vasoactive intestinal polypeptide regulates dynamic changes in astrocyte morphometry: impact on gonadotropin releasing hormone neurons. Endocrinology 147:2197–21202PubMedCrossRefGoogle Scholar
  40. Gerhold LM, Rosewell KL, Wise PM (2005) Suppression of vasoactive intestinal polypeptide in the suprachiasmatic nucleus leads to aging-like alterations in cAMP rhythms and activation of gonadotropin-releasing hormone neurons. J Neurosci 25:62–67PubMedCrossRefGoogle Scholar
  41. Gerkema MP, Shinohara K, Kimura F (1999) Lack of circadian patterns in vasoactive intestinal polypeptide release and variability in vasopressin release in vole suprachiasmatic nuclei in vitro. Neurosci Lett 259:107–110PubMedCrossRefGoogle Scholar
  42. Graham ES, Littlewood P, Turnbull Y, Mercer JG, Morgan PJ, Barrett P (2005) Neuromedin-U is regulated by the circadian clock in the SCN of the mouse. Eur J Neurosci 21:814–819PubMedCrossRefGoogle Scholar
  43. Green DJ, Gillette R (1982) Circadian rhythm of firing rate from single cells in the rat suprachiasmatic brain slice. Brain Res 245:198–200PubMedCrossRefGoogle Scholar
  44. Gribkoff VK, Pieschl RL, Dudek FE (2003) GABA receptor-mediated inhibition of neuronal activity in rat SCN in vitro: pharmacology and influence of circadian phase. J Neurophysiol 90(3):1438–1448PubMedCrossRefGoogle Scholar
  45. Halassa MM, Haydon PG (2010) Integrated brain circuits: astrocytic networks modulate neuronal activity and behavior. Annu Rev Physiol 72:335–355PubMedCrossRefGoogle Scholar
  46. Harmar AJ, Marston HM, Shen S, Spratt C, West KM, Sheward WJ, Morrison CF, Dorin JR, Piggins HD, Reubi JC et al (2002) The VPAC(2) receptor is essential for circadian function in the mouse suprachiasmatic nuclei. Cell 109:497–508PubMedCrossRefGoogle Scholar
  47. Hastings MH (1997) Central clocking. Trends Neurosci 20:459–464PubMedCrossRefGoogle Scholar
  48. Hatcher NG, Atkins N, Annangudi SP, Forbes AJ, Kelleher NL, Gillette MU, Sweedler JV (2008) Mass spectrometry-based discovery of circadian peptides. Proc Natl Acad Sci USA 105:12527–12532PubMedCrossRefGoogle Scholar
  49. Hattar S, Liao HW, Takao M, Berson DM, Yau KW (2002) Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 295:1065–1070PubMedCrossRefGoogle Scholar
  50. Haydon PG (2001) GLIA: listening and talking to the synapse. Nat Rev Neurosci 2:185–193PubMedCrossRefGoogle Scholar
  51. Herzog ED, Huckfeldt RM (2003) Circadian entrainment to temperature, but not light, in the isolated suprachiasmatic nucleus. J Neurophysiol 90:763–770PubMedCrossRefGoogle Scholar
  52. Herzog ED, Geusz ME, Khalsa SBS, Straume M, Block GD (1997) Circadian rhythms in mouse suprachiasmatic nucleus explants on multimicroelectrode plates. Brain Res 757:285–290PubMedCrossRefGoogle Scholar
  53. Herzog ED, Takahashi JS, Block GD (1998) Clock controls circadian period in isolated suprachiasmatic nucleus neurons. Nat Neurosci 1:708–713PubMedCrossRefGoogle Scholar
  54. Honma S, Katsuno Y, Tanahashi Y, Abe H, Honma KI (1998a) Circadian rhythms of arginine-vasopressin and vasoactive intestinal polypeptide do not depend on cytoarchitecture of dispersed cell culture rat suprachiasmatic nucleus. Neuroscience 86:967–976PubMedCrossRefGoogle Scholar
  55. Honma S, Shirakawa T, Katsuno Y, Namihira M, Honma KI (1998b) Circadian periods of single suprachiasmatic neurons in rats. Neurosci Lett 250:157–160PubMedCrossRefGoogle Scholar
  56. Ingram CD, Snowball RK, Mihai R (1996) Circadian rhythm of neuronal activity in suprachiasmatic nucleus slices from the vasopressin-deficient Brattleboro rat. Neuroscience 75:635–641PubMedCrossRefGoogle Scholar
  57. Inouye ST, Kawamura H (1982) Characteristics of a circadian pacemaker in the suprachiasmatic nucleus. J Comp Physiol A 146:153–160CrossRefGoogle Scholar
  58. Irwin RP, Allen CN (2009) GABAergic signaling induces divergent neuronal Ca2+ responses in the suprachiasmatic nucleus network. Eur J Neurosci 30:1462–1475PubMedCrossRefGoogle Scholar
  59. Irwin RP, Allen CN (2010) Neuropeptide-mediated calcium signaling in the suprachiasmatic nucleus network. Eur J Neurosci 32:1497–1506PubMedCrossRefGoogle Scholar
  60. Ishikawa M, Mizobuchi M, Takahashi H, Bando H, Saito S (1997) Somatostatin release as measured by in vivo microdialysis: circadian variation and effect of prolonged food deprivation. Brain Res 749:226–231PubMedCrossRefGoogle Scholar
  61. Jansen K, Van der Zee EA, Gerkema MP (2007) Vasopressin immunoreactivity, but not vasoactive intestinal polypeptide, correlates with expression of circadian rhythmicity in the suprachiasmatic nucleus of voles. Neuropeptides 41(4):207–216PubMedCrossRefGoogle Scholar
  62. Jin X, Shearman LP, Weaver DR, Zylka MJ, De Vries GJ, Reppert SM (1999) A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock. Cell 96:57–68PubMedCrossRefGoogle Scholar
  63. Kalamatianos T, Kalló I, Piggins HD, Coen CW (2004) Expression of VIP and/or PACAP receptor mRNA in peptide synthesizing cells within the suprachiasmatic nucleus of the rat and in its efferent target sites. J Comp Neurol 475:19–35PubMedCrossRefGoogle Scholar
  64. Kallingal GJ, Mintz EM (2006) Glutamatergic activity modulates the phase-shifting effects of gastrin-releasing peptide and light. Eur J Neurosci 24:2853–2858PubMedCrossRefGoogle Scholar
  65. Kallo II, Kalamatianos T, Wiltshire N, Shen S, Sheward WJ, Harmar AJ, Coen CW (2004) Transgenic approach reveals expression of the VPAC receptor in phenotypically defined neurons in the mouse suprachiasmatic nucleus and in its efferent target sites. Eur J Neurosci 19:2201–2211PubMedCrossRefGoogle Scholar
  66. Karatsoreos IN, Yan L, LeSauter J, Silver R (2004) Phenotype matters: identification of light-responsive cells in the mouse suprachiasmatic nucleus. J Neurosci 24:68–75PubMedCrossRefGoogle Scholar
  67. Karatsoreos IN, Romeo RD, McEwen BS, Silver R (2006) Diurnal regulation of the gastrin-releasing peptide receptor in the mouse circadian clock. Eur J Neurosci 23:1047–1053PubMedCrossRefGoogle Scholar
  68. Kim DY, Kang HC, Shin HC, Lee KJ, Yoon YW, Han HC, Na HS, Hong SK, Kim YI (2001) Substance p plays a critical role in photic resetting of the circadian pacemaker in the rat hypothalamus. J Neurosci 21:4026–4031PubMedGoogle Scholar
  69. Klein DC, Moore RY, Reppert SM (1991) Suprachiasmatic nucleus: the mind’s clock. Oxford University Press, New YorkGoogle Scholar
  70. Kramer A, Yang FC, Snodgrass P, Li X, Scammell TE, Davis FC, Weitz CJ (2001) Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling. Science 294:2511–2515PubMedCrossRefGoogle Scholar
  71. Kraves S, Weitz CJ (2006) A role for cardiotrophin-like cytokine in the circadian control of mammalian locomotor activity. Nat Neurosci 9:212–219PubMedCrossRefGoogle Scholar
  72. Laemle LK, Ottenweller JE, Fugaro C (1995) Diurnal variations in vasoactive intestinal polypeptide-like immunoreactivity in the suprachiasmatic nucleus of congenitally anophthalmic mice. Brain Res 688:203–208PubMedCrossRefGoogle Scholar
  73. Landolt HP, Dijk DJ, Gaus SE, Borbely AA (1995) Caffeine reduces low-frequency delta activity in the human sleep EEG. Neuropsychopharmacology 12:229–238PubMedCrossRefGoogle Scholar
  74. Lavialle M, Serviere J (1993) Circadian fluctuations in GFAP distribution in the Syrian hamster suprachiasmatic nucleus. Neuroreport 4:1243–1246PubMedCrossRefGoogle Scholar
  75. Leak RK, Moore RY (2001) Topographic organization of suprachiasmatic nucleus projection neurons. J Comp Neurol 433:312–334PubMedCrossRefGoogle Scholar
  76. Lee JE, Atkins N, Hatcher NG, Zamdborg L, Gillette MU, Sweedler JV, Kelleher NL (2010) Endogenous peptide discovery of the rat circadian clock: a focused study of the suprachiasmatic nucleus by ultrahigh performance tandem mass spectrometry. Mol Cell Proteomics 9:285–297PubMedCrossRefGoogle Scholar
  77. LeSauter J, Stevens P, Jansen H, Lehman MN, Silver R (1999) Calbindin expression in the hamster SCN is influenced by circadian genotype and by photic conditions. Neuroreport 10:3159–3163PubMedCrossRefGoogle Scholar
  78. Li J-D, Burton KJ, Zhang C, Hu S-B, Zhou Q-Y (2009) Vasopressin receptor V1a regulates circadian rhythms of locomotor activity and expression of clock-controlled genes in the suprachiasmatic nuclei. Am J Physiol Regul Integr Comp Physiol 296:R824–R830PubMedCrossRefGoogle Scholar
  79. Liu C, Reppert SM (2000) GABA synchronizes clock cells within the suprachiasmatic circadian clock. Neuron 25:123–128PubMedCrossRefGoogle Scholar
  80. Liu AC, Welsh DK, Ko CH, Tran HG, Zhang EE, Priest AA, Buhr ED, Singer O, Meeker K, Verma IM et al (2007) Intercellular coupling confers robustness against mutations in the SCN circadian clock network. Cell 129:605–616PubMedCrossRefGoogle Scholar
  81. Malarkey EB, Parpura V (2008) Mechanisms of glutamate release from astrocytes. Neurochem Int 52:142–154PubMedCrossRefGoogle Scholar
  82. Marpegan L, Krall TJ, Herzog ED (2009) Vasoactive intestinal polypeptide entrains circadian rhythms in astrocytes. J Biol Rhythms 24:135–143PubMedCrossRefGoogle Scholar
  83. Marpegan L, Swanstrom AE, Chung K, Simon T, Haydon PG, Khan SK, Liu AC, Herzog ED, Beaulé C (2011) Circadian regulation of ATP release in astrocytes. J Neurosci (the official journal of the Society for Neuroscience) 31:8342–8350CrossRefGoogle Scholar
  84. Maywood ES, Reddy AB, Wong GK, O’Neill JS, O’Brien JA, McMahon DG, Harmar AJ, Okamura H, Hastings MH (2006) Synchronization and maintenance of timekeeping in suprachiasmatic circadian clock cells by neuropeptidergic signaling. Curr Biol 16:599–605PubMedCrossRefGoogle Scholar
  85. Maywood ES, Chesham JE, Meng Q-J, Nolan PM, Loudon ASI, Hastings MH (2011a) Tuning the period of the mammalian circadian clock: additive and independent effects of CK1εTau and Fbxl3Afh mutations on mouse circadian behavior and molecular pacemaking. J Neurosci 31:1539–1544PubMedCrossRefGoogle Scholar
  86. Maywood ES, Chesham JE, O’Brien JA, Hastings MH (2011b) A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits. Proc Natl Acad Sci USA 108:14306–14311PubMedCrossRefGoogle Scholar
  87. Meijer JH, Watanabe K, Schaap J, Albus H, Detari L (1998) Light responsiveness of the suprachiasmatic nucleus: long-term multiunit and single-unit recordings in freely moving rats. J Neurosci 18:9078–9087PubMedGoogle Scholar
  88. Michel S, Geusz ME, Zaritsky JJ, Block GD (1993) Circadian rhythm in membrane conductance expressed in isolated neurons. Science 259:239–241PubMedCrossRefGoogle Scholar
  89. Mihalcescu I, Hsing W, Leibler S (2004) Resilient circadian oscillator revealed in individual cyanobacteria. Nature 430:81–85PubMedCrossRefGoogle Scholar
  90. Moore RY, Eichler VB (1972) Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in rat. Brain Res 42:201–206PubMedCrossRefGoogle Scholar
  91. Moore RY, Speh JC, Leak RK (2002) Suprachiasmatic nucleus organization. Cell Tissue Res 309:89–98PubMedCrossRefGoogle Scholar
  92. Mori K, Miyazato M, Ida T, Murakami N, Serino R, Ueta Y, Kojima M, Kangawa K (2005) Identification of neuromedin S and its possible role in the mammalian circadian oscillator system. EMBO J 24(2):325–335PubMedCrossRefGoogle Scholar
  93. Morin LP (2007) SCN organization reconsidered. J Biol Rhythms 22:3–13PubMedCrossRefGoogle Scholar
  94. Moriya T, Yoshinobu Y, Kouzu Y, Katoh A, Gomi H, Ikeda M, Yoshioka T, Itohara S, Shibata S (2000) Involvement of glial fibrillary acidic protein (GFAP) expressed in astroglial cells in circadian rhythm under constant lighting conditions in mice. J Neurosci Res 60:212–218PubMedCrossRefGoogle Scholar
  95. Murakami N, Takamure M, Takahashi K, Utunomiya K, Kuroda H, Etoh T (1991) Long-term cultured neurons from rat suprachiasmatic nucleus retain the capacity for circadian oscillation of vasopressin release. Brain Res 545:347–350PubMedCrossRefGoogle Scholar
  96. Nakamura W, Honma S, Shirakawa T, Honma KI (2001) Regional pacemakers composed of multiple oscillator neurons in the rat suprachiasmatic nucleus. Eur J Neurosci 14:1–10CrossRefGoogle Scholar
  97. Nakamura W, Honma S, Shirakawa T, Honma KI (2002) Clock mutation lengthens the circadian period without damping rhythms in individual SCN neurons. Nat Neurosci 5:399–400PubMedGoogle Scholar
  98. Ng FS, Tangredi MM, Jackson FR (2011) Glial cells physiologically modulate clock neurons and circadian behavior in a calcium-dependent manner. Curr Biol 21:625–634PubMedCrossRefGoogle Scholar
  99. Nitabach MN, Taghert PH (2008) Organization of the Drosophila circadian control circuit. Curr Biol 18:R84–R93PubMedCrossRefGoogle Scholar
  100. Oike H, Kobori M, Suzuki T, Ishida N (2011) Caffeine lengthens circadian rhythms in mice. Biochem Biophys Res Commun 410:654–658PubMedCrossRefGoogle Scholar
  101. Parpura V, Zorec R (2010) Gliotransmission: exocytotic release from astrocytes. Brain Res Rev 63:83–92PubMedCrossRefGoogle Scholar
  102. Pennartz CMA, de Jeu MTG, Bos NPA, Schaap J, Geurtsen AMS (2002) Diurnal modulation of pacemaker potentials and calcium current in the mammalian circadian clock. Nature 416:286–290PubMedCrossRefGoogle Scholar
  103. Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32:421–431PubMedCrossRefGoogle Scholar
  104. Piggins HD, Antle MC, Rusak B (1995) Neuropeptides phase shift the mammalian circadian pacemaker. J Neurosci 15:5612–5622PubMedGoogle Scholar
  105. Portaluppi F, Tiseo R, Smolensky MH, Hermida RC, Ayala DE, Fabbian F (2012) Circadian rhythms and cardiovascular health. Sleep Med Rev 16:151–166PubMedCrossRefGoogle Scholar
  106. Prolo LM, Takahashi JS, Herzog ED (2005) Circadian rhythm generation and entrainment in astrocytes. J Neurosci 25:404–408PubMedCrossRefGoogle Scholar
  107. Quintero JE, Kuhlman SJ, McMahon DG (2003) The biological clock nucleus: a multiphasic oscillator network regulated by light. J Neurosci 23:8070–8076PubMedGoogle Scholar
  108. Ralph MR, Foster RG, Davis FC, Menaker M (1990) Transplanted suprachiasmatic nucleus determines circadian period. Science 247:975–978PubMedCrossRefGoogle Scholar
  109. Reed HE, Meyer-Spasche A, Cutler DJ, Coen CW, Piggins HD (2001) Vasoactive intestinal polypeptide (VIP) phase-shifts the rat suprachiasmatic nucleus clock in vitro. Eur J Neurosci 13:839–843PubMedCrossRefGoogle Scholar
  110. Reppert SM, Artman HG, Swaminathan S, Fisher DA (1981) Vasopressin exhibits a rhythmic daily pattern in cerebrospinal fluid but not in blood. Science 213:1256–1257PubMedCrossRefGoogle Scholar
  111. Ribelayga C, Cao Y, Mangel SC (2008) The circadian clock in the retina controls rod-cone coupling. Neuron 59:790–801PubMedCrossRefGoogle Scholar
  112. Robinson BG, Frim DM, Schwartz WJ, Majzoub JA (1988) Vasopressin mRNA in the suprachiasmatic nuclei: daily regulation of polyadenylate tail length. Science 241:342–344PubMedCrossRefGoogle Scholar
  113. Rusnak M, Tóth ZE, House SB, Gainer H (2007) Depolarization and neurotransmitter regulation of vasopressin gene expression in the rat suprachiasmatic nucleus in vitro. J Neurosci 27:141–151PubMedCrossRefGoogle Scholar
  114. Shigeyoshi Y, Taguchi K, Yamamoto S, Takekida S, Yan L, Tei H, Moriya T, Shibata S, Loros JJ, Dunlap JC et al (1997) Light-induced resetting of a mammalian circadian clock is associated with rapid induction of the mPer1 transcript. Cell 91:1043–1053PubMedCrossRefGoogle Scholar
  115. Shinohara K, Tominaga K, Isobe Y, Inouye ST (1993) Photic regulation of peptides located in the ventrolateral subdivision of the suprachiasmatic nucleus of the rat: daily variations of vasoactive intestinal polypeptide, gastrin-releasing peptide, and neuropeptide Y. J Neurosci 13:793–800PubMedGoogle Scholar
  116. Shinohara K, Honma S, Katsuno Y, Abe H, Honma KI (1995) Two distinct oscillators in the rat suprachiasmatic nucleus in vitro. Proc Natl Acad Sci USA 92:7396–7400PubMedCrossRefGoogle Scholar
  117. Shinohara K, Tominaga K, Inouye ST (1998) Luminance-dependent decrease in vasoactive intestinal polypeptide in the rat suprachiasmatic nucleus. Neurosci Lett 251:21–24PubMedCrossRefGoogle Scholar
  118. Shinohara K, Honma S, Katsuno Y, Honma K (2000) Circadian release of excitatory amino acids in the suprachiasmatic nucleus culture is Ca(2+)-independent. Neurosci Res 36:245–250PubMedCrossRefGoogle Scholar
  119. Silver R, Lehman MN, Gibson M, Gladstone WR, Bittman EL (1990) Dispersed cell suspensions of fetal SCN restore circadian rhythmicity in SCN-lesioned adult hamsters. Brain Res 525:45–58PubMedCrossRefGoogle Scholar
  120. Sodersten P, De Vries GJ, Buijs RM, Melin P (1985) A daily rhythm in behavioral vasopressin sensitivity and brain vasopressin concentrations. Neurosci Lett 58:37–41PubMedCrossRefGoogle Scholar
  121. Stephan FK, Zucker I (1972) Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. Proc Natl Acad Sci USA 69:1583–1586PubMedCrossRefGoogle Scholar
  122. Suadicani SO, Brosnan CF, Scemes E (2006) P2X7 receptors mediate ATP release and amplification of astrocytic intercellular Ca2+ signaling. J Neurosci 26:1378–1385PubMedCrossRefGoogle Scholar
  123. Suh J, Jackson FR (2007) Drosophila ebony activity is required in glia for the circadian regulation of locomotor activity. Neuron 55:435–447PubMedCrossRefGoogle Scholar
  124. Sujino M, Masumoto K, Yamaguchi S, van der Horst GT, Okamura H, Inouye SI (2003) Suprachiasmatic nucleus grafts restore circadian behavioral rhythms of genetically arrhythmic mice. Curr Biol 13:664–668PubMedCrossRefGoogle Scholar
  125. Swaab DF, Pool CW, Nijveldt F (1975) Immunofluorescence of vasopressin and oxytocin in the rat hypothalamo-neurohypophypopseal system. J Neural Transm 36:195–215PubMedCrossRefGoogle Scholar
  126. Tominaga K, Shinohara K, Otori Y, Fukuhara C, Inouye ST (1992) Circadian rhythms of vasopressin content in the suprachiasmatic nucleus of the rat. Neuroreport 3:809–812PubMedCrossRefGoogle Scholar
  127. Tousson E, Meissl H (2004) Suprachiasmatic nuclei grafts restore the circadian rhythm in the paraventricular nucleus of the hypothalamus. J Neurosci 24:2983–2988PubMedCrossRefGoogle Scholar
  128. Usdin TB, Bonner TI, Mezey E (1994) Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions. Endocrinology 135:2662–2680PubMedCrossRefGoogle Scholar
  129. Vandesande F, DeMey J, Dierickx K (1974) Identification of neurophysin producing cells. I. The origin of the neurophysin-like substance-containing nerve fibres of the external region of the median eminence of the rat. Cell Tissue Res 151:187–200PubMedCrossRefGoogle Scholar
  130. Vosko AM, Schroeder A, Loh DH, Colwell CS (2007) Vasoactive intestinal peptide and the mammalian circadian system. Gen Comp Endocrinol 152:165–175PubMedCrossRefGoogle Scholar
  131. Wagner S, Castel M, Gainer H, Yarom Y (1997) GABA in the mammalian suprachiasmatic nucleus and its role in diurnal rhythmicity. Nature 387:598–603PubMedCrossRefGoogle Scholar
  132. Wallén P, Christenson J, Brodin L, Hill R, Lansner A, Grillner S (1989) Mechanisms underlying the serotonergic modulation of the spinal circuitry for locomotion in lamprey. Prog Brain Res 80:321–327, discussion 315–319PubMedCrossRefGoogle Scholar
  133. Webb AB, Angelo N, Huettner JE, Herzog ED (2009) Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons. Proc Natl Acad Sci USA 106:16493–16498PubMedCrossRefGoogle Scholar
  134. Welsh DK, Logothetis DE, Meister M, Reppert SM (1995) Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms. Neuron 14:697–706PubMedCrossRefGoogle Scholar
  135. Welsh DK, Takahashi JS, Kay SA (2010) Suprachiasmatic nucleus: cell autonomy and network properties. Annu Rev Physiol 72:551–577PubMedCrossRefGoogle Scholar
  136. Womac AD, Burkeen JF, Neuendorff N, Earnest DJ, Zoran MJ (2009) Circadian rhythms of extracellular ATP accumulation in suprachiasmatic nucleus cells and cultured astrocytes. Eur J Neurosci 30:869–876PubMedCrossRefGoogle Scholar
  137. Wright KP, Badia P, Myers BL, Plenzler SC (1997) Combination of bright light and caffeine as a countermeasure for impaired alertness and performance during extended sleep deprivation. J Sleep Res 6:26–35PubMedCrossRefGoogle Scholar
  138. Wyatt JK, Cajochen C, Ritz-De Cecco A, Czeisler CA, Dijk DJ (2004) Low-dose repeated caffeine administration for circadian-phase-dependent performance degradation during extended wakefulness. Sleep 27:374–381PubMedGoogle Scholar
  139. Yamaguchi S, Isejima H, Matsuo T, Okura R, Yagita K, Kobayashi M, Okamura H (2003) Synchronization of cellular clocks in the suprachiasmatic nucleus. Science 302:1408–1412PubMedCrossRefGoogle Scholar
  140. Yamazaki S, Ishida Y, Inouye S (1994) Circadian rhythms of adenosine triphosphate contents in the suprachiasmatic nucleus, anterior hypothalamic area and caudate putamen of the rat–negative correlation with electrical activity. Brain Res 664:237–240PubMedCrossRefGoogle Scholar
  141. Yamazaki S, Kerbeshian MC, Hocker CG, Block GD, Menaker M (1998) Rhythmic properties of the hamster suprachiasmatic nucleus in vivo. J Neurosci 18:10709–10723PubMedGoogle Scholar
  142. Yamazaki S, Numano R, Abe M, Hida A, Takahashi R, Ueda M, Block GD, Sakaki Y, Menaker M, Tei H (2000) Resetting central and peripheral circadian oscillators in transgenic rats. Science 288:682–685PubMedCrossRefGoogle Scholar
  143. Zhou QY, Cheng MY (2005) Prokineticin 2 and circadian clock output. FEBS J 272:5703–5709PubMedCrossRefGoogle Scholar
  144. Zusev M, Gozes I (2004) Differential regulation of activity-dependent neuroprotective protein in rat astrocytes by VIP and PACAP. Regul Pept 123:33–41PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of BiologyWashington UniversitySt. LouisUSA

Personalised recommendations