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The Circadian Clock and the Homeostatic Hourglass: Two Timepieces Controlling Sleep and Wakefulness

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Book cover The Circadian Clock

Part of the book series: Protein Reviews ((PRON,volume 12))

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Abstract

Sleep is controlled by the interplay of two internal oscillators: the circadian pacemaker and the sleep homeostat. These two facets of sleep regulation play a pivotal role in the prediction of sleep propensity in humans on a wide array of dimensions: sleep timing and duration, REM sleep, non-REM sleep, REM density, sleep spindles, slow-wave sleep, slow-wave activity, etc. The relative contribution of these oscillators crucially relies on their nonadditive contribution, and, thus, on the repercussions that one process has on each other. Here, we present evidence on how the circadian timing system and its neuroanatomical underpinnings regulate the timing of sleep and wakefulness. The role of the sleep/wake homeostat for sleep consolidation, together with a possible functional role of this process in synaptic downscaling will be explained. Furthermore, we summarize recent studies on the complex interplay of the two sleep oscillators, with respect to electroencephalographic activity, molecular genetic correlates, like clock genes polymorphisms, and its implications on healthy aging and on clinical scenarios. Understanding the tug of war between the circadian clock and the sleep homeostat in the control for sleep is a prerequisite for treating sleep disturbances in a variety of physical and/or mental disorders.

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References

  1. Dijk DJ, Von Schantz M (2005) Timing and consolidation of human sleep, wakefulness, and performance by a symphony of oscillators. J Biol Rhythms 20:279–290

    Article  PubMed  Google Scholar 

  2. Cajochen C, Dijk DJ (2003) Electroencephalographic activity during wakefulness, rapid eye movement and non-rapid eye movement sleep in humans: Comparison of their circadian and homeostatic modulation. Sleep Biol Rhythms 1:85–95

    Article  Google Scholar 

  3. Moore RY, Speh JC, Leak RK (2002) Suprachiasmatic nucleus organization. Cell Tissue Res 309:89–98

    Article  PubMed  CAS  Google Scholar 

  4. Czeisler CA, Duffy JF, Shanahan TL, Brown EN, Mitchell JF, Rimmer DW, Ronda JM, Silva EJ, Allan JS, Emens JS, Dijk DJ, Kronauer RE (1999) Stability, precision, and near-24-hour period of the human circadian pacemaker. Science 284:2177–2181

    Article  PubMed  CAS  Google Scholar 

  5. Gachon F, Nagoshi E, Brown SA, Ripperger J, Schibler U (2004) The mammalian circadian timing system: from gene expression to physiology. Chromosoma 113:103–112

    Article  PubMed  Google Scholar 

  6. Schibler U, Sassone-Corsi P (2002) A web of circadian pacemakers. Cell 111:919–922

    Article  PubMed  CAS  Google Scholar 

  7. Hastings MH, Herzog ED (2004) Clock genes, oscillators, and cellular networks in the suprachiasmatic nuclei. J Biol Rhythms 19:400–413

    Article  PubMed  CAS  Google Scholar 

  8. Moore RY (1997) Circadian rhythms: basic neurobiology and clinical applications. Annu Rev Med 48:253–266

    Article  PubMed  CAS  Google Scholar 

  9. Borbély AA (1982) A two process model of sleep regulation. Hum Neurobiol 1:195–204

    PubMed  Google Scholar 

  10. Tononi G, Cirelli C (2006) Sleep function and synaptic homeostasis. Sleep Med Rev 10:49–62

    Article  PubMed  Google Scholar 

  11. Tononi G, Cirelli C (2003) Sleep and synaptic homeostasis: a hypothesis. Brain Res Bull 62:143–150

    Article  PubMed  Google Scholar 

  12. Cajochen C, Wyatt JK, Czeisler CA, Dijk DJ (2002) Separation of circadian and wake duration-dependent modulation of EEG activation during wakefulness. Neuroscience 114:1047–1060

    PubMed  CAS  Google Scholar 

  13. Dijk DJ (1999) Reply to technical note: nonlinear interactions between circadian and homeostatic processes: models or metrics? J Biol Rhythms 14:604–605

    Article  PubMed  CAS  Google Scholar 

  14. Czeisler CA, Buxton OM, Khalsa SBS (2005) The human circadian timing system and sleep–wake regulation. In: Kryger MH, Roth T, Dement W (eds) Principles and practice of sleep medicine, 4th edn. Philadelphia, Elsevier, pp 375–394

    Google Scholar 

  15. Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941

    Article  PubMed  CAS  Google Scholar 

  16. Moore RY (1983) Organization and function of a central nervous system circadian oscillator: the suprachiasmatic hypothalamic nucleus. Fed Proc 42:2783–2789

    PubMed  CAS  Google Scholar 

  17. Klein DC, Moore RY, Reppert SM (1991) Suprachiasmatic nucleus: the mind’s clock. Oxford University Press, New York

    Google Scholar 

  18. Berson DM, Dunn FA, Takao M (2002) Phototransduction by retinal ganglion cells that set the circadian clock. Science 295:1070–1073

    Article  PubMed  CAS  Google Scholar 

  19. Provencio I, Rodriguez IR, Jiang G, Hayes WP, Moreira EF, Rollag MD (2000) A novel human opsin in the inner retina. J Neurosci 20:600–605

    PubMed  CAS  Google Scholar 

  20. Wirz-Justice A (2007) How to measure circadian rhythms in human. Medicographia 29:84–90

    Google Scholar 

  21. Lockley SW, Skene DJ, James K, Thapan K, Wright J, Arendt J (2000) Melatonin administration can entrain the free-running circadian system of blind subjects. J Endocrinol 164:R1–R6

    Article  PubMed  CAS  Google Scholar 

  22. Berson DM (2003) Strange vision: ganglion cells as circadian photoreceptors. Trends Neurosci 26:314–320

    Article  PubMed  CAS  Google Scholar 

  23. Provencio I, Rollag MD, Castrucci AM (2002) Photoreceptive net in the mammalian retina. Nature 415:493–494

    Article  PubMed  CAS  Google Scholar 

  24. Moore RY, Lenn NJ (1972) A retinohypothalamic projection in the rat. J Comp Neurol 146:1–9

    Article  PubMed  CAS  Google Scholar 

  25. Meyer-Bernstein EL, Morin LP (1996) Differential serotonergic innervation of the suprachiasmatic nucleus and the intergeniculate leaflet and its role in circadian rhythm modulation. J Neurosci 16:2097–2111

    PubMed  CAS  Google Scholar 

  26. Cohen RA, Albers HE (1991) Disruption of human circadian and cognitive regulation following a discrete hypothalamic lesion: a case study. Neurology 41:726–729

    PubMed  CAS  Google Scholar 

  27. Inouye ST, Kawamura H (1979) Persistence of circadian rhythmicity in a mamalian hypothalamic “island” containing the suprachiasmatic nucleus. Proc Natl Acad Sci U S A 76:5962–5966

    Article  PubMed  CAS  Google Scholar 

  28. Moore R (2007) Suprachiasmatic nucleus in sleep–wake regulation. Sleep Med 8:27–33

    Article  PubMed  Google Scholar 

  29. Saper CB, Chou TC, Scammell TE (2001) The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci 24:726–731

    Article  PubMed  CAS  Google Scholar 

  30. Mc Carley RW (2007) Neurobiology of REM and NREM sleep. Sleep Med 8:302–330

    Article  Google Scholar 

  31. Llinas R, Steriade M (2006) Bursting of thalamic neurons and states of vigilance. J Neurophysiol 95:3297–3308

    Article  PubMed  Google Scholar 

  32. Abrahamson EE, Leak RK, Moore RY (2001) The suprachiasmatic nucleus projects to posterior hypothalamic arousal systems. Neuroreport 12:435–440

    Article  PubMed  CAS  Google Scholar 

  33. Deboer T, Overeem S, Visser NAH, Duindam H, Frölich M, Lammers GJ, Meijer JH (2004) Convergence of circadian and sleep regulatory mechanisms on hypocretin-1. Neuroscience 129:727–732

    Article  PubMed  CAS  Google Scholar 

  34. Yoshida Y, Fujiki N, Nakajima T, Ripley B, Matsumura H, Yoneda H, Mignot E, Nishino S (2001) Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light–dark cycle and sleep–wake activities. Eur J Neurosci 14:1075–1081

    Article  PubMed  CAS  Google Scholar 

  35. Zeitzer JM, Buckmaster CL, Parker KJ, Hauck CM, Lyons DM, Mignot E (2003) Circadian and homeostatic regulation of hypocretin in a primate model: implications for the consolidation of wakefulness. J Neurosci 23:3555–3560

    PubMed  CAS  Google Scholar 

  36. Brisbare-Roch C, Dingemanse J, Koberstein R, Hoever P, Aissaoui H, Flores S (2007) Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nature 12:150–155

    Google Scholar 

  37. Mistlberger RE (2005) Circadian regulation of sleep in mammals: role of the suprachiasmatic nucleus. Brain Res Rev 49:429–454

    Article  PubMed  Google Scholar 

  38. Moore RY (1996) Neural control of the pineal gland. Behav Brain Res 73:125–130

    Article  PubMed  CAS  Google Scholar 

  39. Czeisler CA, Gooley J (2007) Sleep and circadian rhythms in humans. Cold Spring Harb Symp Quant Biol 72:579–597

    Article  PubMed  CAS  Google Scholar 

  40. Cajochen C, Münch M, Knoblauch V, Blatter K, Wirz-Justice A (2006) Age-related changes in the circadian and homeostatic regulation of human sleep. Chronobiol Int 23:1–14

    Article  Google Scholar 

  41. Dibner C, Sage D, Unser M, Bauer C, d’Esmond T, Naef F, Schibler U (2008) Circadian gene expression is resilient to large fluctuations in overall transcription rates. EMBO J. 21;28(2):123–134

    Google Scholar 

  42. Schibler U, Ripperger J, Brown SA (2003) Peripheral circadian oscillators in mammals: time and food. J Biol Rhythms 18:250–260

    Article  PubMed  Google Scholar 

  43. Mc Carley RW, Massaquoi SG (1992) Neurobiological structure of the revised limit cycle reciprocal interaction model of REM cycle control. J Sleep Res 1:132–137

    Article  Google Scholar 

  44. Saper CB, Cano G, Scammell TE (2005) Homeostatic, circadian, and emotional regulation of sleep. J Comp Neurol 493:92–98

    Article  PubMed  CAS  Google Scholar 

  45. Saper CB, Scammell TE, Lu J (2005) Hypothalamic regulation of sleep and circadian rhythms. Nature 437:1257–1263

    Article  PubMed  CAS  Google Scholar 

  46. Chou TC, Scammell TE, Gooley JJ, Gaus SE, Saper CB, Lu J (2003) Critical role of dorsomedial hypothalamic nucleus in a wide range of behavioral circadian rhythms. J Neurosci 23:10691–10702

    PubMed  CAS  Google Scholar 

  47. Dijk DJ, Duffy JF, Czeisler CA (1992) Circadian and sleep/wake dependent aspects of subjective alertness and cognitive performance. J Sleep Res 1:112–117

    Article  PubMed  CAS  Google Scholar 

  48. Dijk DJ (1995) EEG slow waves and sleep spindles: windows on the sleeping brain. Behav Brain Res 69:109–116

    Article  PubMed  CAS  Google Scholar 

  49. Jewett ME, Rimmer DW, Duffy JF, Klerman EB, Kronauer RE, Czeisler CA (1997) Human circadian pacemaker is sensitive to light throughout subjective day without evidence of transients. Am J Physiol Regul Integr Comp Physiol 273:R1800–R1809

    CAS  Google Scholar 

  50. Van Dongen HPA, Maislin G, Mullington JM, Dinges DF (2003) The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep 26:117–126

    PubMed  Google Scholar 

  51. Lockley SW, Cronin JW, Evans EE, Cade BE, Lee CJ, Landrigan CP, Rothschild JM, Katz JT, Lilly CM, Stone PH, Aeschbach D, Czeisler CA, the Harvard Work Hours, H.A.S.G. (2004) Effect of reducing interns’ weekly work hours on sleep and attentional failures. N Engl J Med 351:1829–1837

    Google Scholar 

  52. Brunner DP, Dijk DJ, Borbély AA (1993) Repeated partial sleep deprivation progressively changes the EEG during sleep and wakefulness. Sleep 16:100–113

    PubMed  CAS  Google Scholar 

  53. Dijk DJ, Hayes B, Czeisler CA (1993) Dynamics of electroencephalographic sleep spindles and slow wave activity in men: effect of sleep deprivation. Brain Res 626:190–199

    Article  PubMed  CAS  Google Scholar 

  54. Cajochen C, Foy R, Dijk DJ (1999) Frontal predominance of a relative increase in sleep delta and theta EEG activity after sleep loss in humans. Sleep Res Online 2:65–69

    PubMed  CAS  Google Scholar 

  55. Borbély AA, Baumann F, Brandeis D, Strauch I, Lehmann D (1981) Sleep deprivation: effect on sleep stages and EEG power density in man. Electroencephalogr Clin Neurophysiol 51:483–495

    Article  PubMed  Google Scholar 

  56. Cajochen C, Knoblauch V, Kräuchi K, Renz C, Wirz-Justice A (2001) Dynamics of frontal EEG activity, sleepiness and body temperature under high and low sleep pressure. Neuroreport 12:2277–2281

    Article  PubMed  CAS  Google Scholar 

  57. Werth E, Dijk DJ, Achermann P, Borbély AA (1996) Dynamics of the sleep EEG after an early evening nap: experimental data and simulations. Am J Physiol Regul Integr Comp Physiol 271:501–510

    Google Scholar 

  58. Werth E, Achermann P, Borbély AA (1996) Brain topography of the human sleep EEG: Antero-posterior shifts of spectral power. Neuroreport 8:123–127

    Article  PubMed  CAS  Google Scholar 

  59. Finelli LA, Baumann H, Borbély AA, Achermann P (2000) Dual electroencephalogram markers of human sleep homeostasis: correlation between theta activity in waking and slow-wave activity in sleep. Neuroscience 101:523–529

    Article  PubMed  CAS  Google Scholar 

  60. Knoblauch V, Kräuchi K, Renz C, Wirz-Justice A, Cajochen C (2002) Homeostatic control of slow-wave and spindle frequency activity during human sleep: effect of differential sleep pressure and brain topography. Cereb Cortex 12:1092–1100

    Article  PubMed  CAS  Google Scholar 

  61. Borbély AA, Achermann P (2000) Sleep homeostasis and models of sleep regulation. In: Kryger MH, Roth T, Dement WC (eds) Principles and practice of sleep medicine. W B Saunders Company, Philadelphia, pp 377–390

    Google Scholar 

  62. Rétey JV, Adam M, Honegger E, Khatami R, Luhmann UF, Jung HH, Berger W, Landolt HP (2005) A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans. Proc Natl Acad Sci U S A 102:15676–15681

    Article  PubMed  CAS  Google Scholar 

  63. Rétey JV, Adam M, Gottselig JM, Khatami R, Dürr R, Achermann P, Landolt HP (2006) Adenosinergic mechanisms contribute to individual differences in sleep deprivation-induced changes in neurobehavioral function and brain rhythmic activity. J Neurosci 26:10472–10479

    Article  PubMed  CAS  Google Scholar 

  64. Landolt HP (2008) Sleep homeostasis: A role for adenosine in humans? Biochem Pharmacol 75:2070–2079

    Article  PubMed  CAS  Google Scholar 

  65. Huston JP, Haas HL, Boix F, Pfister MUD, Schrader J (1996) Extracellular adenosine levels in neostriatum and hippocampus during rest and activity periods of rats. Neuroscience 73:99–107

    Article  PubMed  CAS  Google Scholar 

  66. Murillo-Rodriguez E, Blanco-Centurion C, Gerashchenko D, Salin-Pascual RJ, Shiromani P (2004) The diurnal rhythm of forebrain of young and adenosine levels in the basal old rats. Neuroscience 123:361–370

    Article  PubMed  CAS  Google Scholar 

  67. Strecker RE, Morairty S, Thakkar MM, Porkka-Heiskanen T, Basheer R, Dauphin LJ (2000) Adenosinergic modulation of basal forebrain and preoptic/anterior hypothalamic neuronal activity in the control of behavioral state. Behav Brain Res 115:183–204

    Article  PubMed  CAS  Google Scholar 

  68. Basheer R, Strecker RE, Thakkar MM, McCarley RW (2004) Adenosine and sleep–wake regulation. Prog Neurobiol 73:379–396

    Article  PubMed  CAS  Google Scholar 

  69. Chamberlin NL, Arrigoni E, Chou TC, Scammell TE, Greene RW, Saper CB (2003) Effects of adenosine on GABAergic synaptic inputs to identified ventrolateral preoptic neurons. Neuroscience 119:913–918

    Article  PubMed  CAS  Google Scholar 

  70. Morairty S, Rainnie D, McCarley R, Greene RW (2004) Disinhibition of ventrolateral preoptic area sleep-active neurons by adenosine: a new mechanism for sleep promotion. Neuroscience 123:451–457

    Article  PubMed  CAS  Google Scholar 

  71. Timofeev I, Grenier F, Steriade M (2001) Disfacilitation and active inhibition in the neocortex during the natural sleep–wake cycle: an intracellular study. Proc Natl Acad Sci U S A 98:1924–1929

    Article  PubMed  CAS  Google Scholar 

  72. Maret S, Dorsaz S, Gurcel L, Pradervand S, Petit B, Pfister C, Hagenbuchle O, O’Hara BF, Franken P, Tafti M (2007) Homer1a is a core brain molecular correlate of sleep loss. Proc Natl Acad Sci U S A 104:20090–20095

    Article  PubMed  Google Scholar 

  73. Compte A, Sanchez-Vives MV, McCormick DA, Wang XJ (2003) Cellular and network mechanisms of slow oscillatory activity (< 1 Hz) and wave propagations in a cortical network model. J Neurophysiol 89:2707–2725

    Article  PubMed  Google Scholar 

  74. Bazhenov M, Timofeev I, Steriade M, Sejnowski TJ (2002) Model of thalamocortical slow-wave sleep oscillations and transitions to activated states. J Neurosci 22:8691–8704

    PubMed  CAS  Google Scholar 

  75. Hill S, Tononi G (2005) Modeling sleep and wakefulness in the thalamocortical system. J Neurophysiol 93:1671–1698

    Article  PubMed  Google Scholar 

  76. Massimini M, Huber R, Ferrarelli F, Hill S, Tononi G (2004) The sleep slow oscillation as a travelling wave. J Neurosci 24:6862–6870

    Article  PubMed  CAS  Google Scholar 

  77. Cajochen C, Brunner DP, Kräuchi K, Graw P, Wirz-Justice A (1995) Power density in theta/alpha frequencies of the waking EEG progressively increases during sustained wakefulness. Sleep 18:890–894

    PubMed  CAS  Google Scholar 

  78. Cajochen C, Kräuchi K, Knoblauch V, Renz C, Rössler A, Balestrieri G, Dattler MF, Graw P, Wirz-Justice A (2001) Dynamics of frontal low EEG-activity, subjective sleepiness and body temperature under high and low sleep pressure. Neuroreport 20;12(10):2277–2281

    Google Scholar 

  79. Aeschbach D, Matthews JR, Postolache TT, Jackson MA, Giesen HA, Wehr TA (1997) Dynamics of the human EEG during prolonged wakefulness: evidence for frequency-specific circadian and homeostatic influences. Neurosci Lett 239:121–124

    Article  PubMed  CAS  Google Scholar 

  80. Dijk DJ, Beersma DGM, Daan S (1987) EEG power density during nap sleep: reflection of an hourglass measuring the duration of prior wakefulness. J Biol Rhythms 2:207–219

    Article  PubMed  CAS  Google Scholar 

  81. Cirelli C, Tononi G (2000) Differential expression of plasticity-related genes in waking and sleep and their regulation by the noradrenergic system. J Neurosci 20:9187–9194

    PubMed  CAS  Google Scholar 

  82. Cirelli C, Pompeiano M, Tononi G (1996) Neuronal gene expression in the waking state: a role for the locus coeruleus. Science 274:1211–1215

    Article  PubMed  CAS  Google Scholar 

  83. Kopp C, Longordo F, Nicholson JR, Lüthi A (2006) Insufficient sleep reversibly alters bidirectional synaptic plasticity and NMDA receptor function. J Neurosci 26:12456–12465

    Article  PubMed  CAS  Google Scholar 

  84. Krueger JM, Obàl F (1993) A neuronal group theory of sleep function. J Sleep Res 2:63–69

    Article  PubMed  Google Scholar 

  85. Krueger JM, Obàl F Jr, Kapàs L, Fang J (1995) Brain organization and sleep function. Behav Brain Res 69:177–185

    Article  PubMed  CAS  Google Scholar 

  86. Vyazovskiy VV, Cirelli C, Pfister-Genskow M, Faraguna U, Tononi G (2008) Molecular and electrophysiological evidence for net synaptic potentiation in wake and depression in sleep. Nat Neurosci 11:200–208

    Article  PubMed  CAS  Google Scholar 

  87. Vyazovskiy VV, Riedner BA, Cirelli C, Tononi G (2007) Sleep homeostasis and cortical synchronization: II. A local field potential study of sleep slow waves in the rat. Sleep 30:1631–1642

    PubMed  Google Scholar 

  88. Grutzendler J, Kasthuri N, Gan WB (2002) Long-term dendritic spine stability in the adult cortex. Nature 420:812–816

    Article  PubMed  CAS  Google Scholar 

  89. Dijk DJ, Edgar DM (1999) Circadian and homeostatic control of wakefulness and sleep. In: Turek FW, Zee PC (eds) Regulation of sleep and circadian rhythms, vol 133. Marcel Dekker, Inc, New York Basel, pp 111–147

    Google Scholar 

  90. Dijk DJ, Czeisler CA (1995) Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans. J Neurosci 15:3526–3538

    PubMed  CAS  Google Scholar 

  91. Kronauer RE, Czeisler CA, Pilato SF, Moore-Ede MC, Weitzman ED (1982) Mathematical model of the human circadian system with two interacting oscillators. Am J Physiol Regul Integr Comp Physiol 242:R3–R17

    CAS  Google Scholar 

  92. Daan S, Beersma DGM, Borbély AA (1984) Timing of human sleep: recovery process gated by a circadian pacemaker. Am J Physiol Regul Integr Comp Physiol 246:R161–R178

    CAS  Google Scholar 

  93. Edgar DM, Dement WC, Fuller CA (1993) Effect of SCN lesions on sleep in squirrel monkeys: evidence for opponent processes in sleep–wake regulation. J Neurosci 13:1065–1079

    PubMed  CAS  Google Scholar 

  94. Cajochen C, Khalsa SBS, Wyatt JK, Czeisler CA, Dijk DJ (1999) EEG and ocular correlates of circadian melatonin phase and human performance decrements during sleep loss. Am J Physiol Regul Integr Comp Physiol 277:R640–R649

    CAS  Google Scholar 

  95. Johnson MP, Duffy JF, Dijk DJ, Ronda JM, Dyal CM, Czeisler CA (1992) Short-term memory, alertness and performance: a reappraisal of their relationship to body temperature. J Sleep Res 1:24–29

    Article  PubMed  CAS  Google Scholar 

  96. Dijk DJ, Czeisler CA (1994) Paradoxical timing of the circadian rhythm of sleep propensity serves to consolidate sleep and wakefulness in humans. Neurosci Lett 166:63–68

    Article  PubMed  CAS  Google Scholar 

  97. Liu C, Weaver D, Jin X, Shearman L, SM R (1997) Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron 19:91

    Article  PubMed  CAS  Google Scholar 

  98. Barinaga M (1997) How jet-lag hormone does double duty in the brain. Science 277:480

    Article  PubMed  CAS  Google Scholar 

  99. Czeisler CA, Zimmerman JC, Ronda JM, Moore-Ede MC, Weitzman ED (1980) Timing of REM sleep is coupled to the circadian rhythm of body temperature in man. Sleep 2:329–346

    PubMed  CAS  Google Scholar 

  100. Tobler I, Borbély AA, Groos G (1983) The effect of sleep deprivation on sleep in rats with suprachiasmatic lesions. Neurosci Lett 21:49–54

    Article  Google Scholar 

  101. Achermann P (1999) Technical note: a problem with identifying nonlinear interactions of circadian and homeostatic processes. J Biol Rhythms 14:602–603

    Article  PubMed  CAS  Google Scholar 

  102. Deboer T, Vansteensel MJ, Détari L, Meijer JH (2003) Sleep states alter activity of suprachiasmatic nucleus neurons. Nat Neurosci 6:1086–1090

    Article  PubMed  CAS  Google Scholar 

  103. Zulley J, Wever R, Aschoff J (1981) The dependence of onset and duration of sleep on the circadian rhythm of rectal temperature. Pflügers Arch 391:314–318

    PubMed  CAS  Google Scholar 

  104. Aschoff J, Von Goetz C, Wildgruber C, Wever RA (1986) Meal timing in humans during isolation without time cues. J Biol Rhythms 1:151–162

    Article  PubMed  CAS  Google Scholar 

  105. Aschoff J, Gerecke U, Wever R (1967) Desynchronization of human circadian rhythms. Jpn J Physiol 17:450–457

    PubMed  CAS  Google Scholar 

  106. Zulley J (1980) Distribution of REM sleep in entrained 24 hour and free-running sleep–wake cycles. Sleep 2:377–389

    PubMed  CAS  Google Scholar 

  107. Zimmerman JC, Czeisler CA, Laxminarayan S, Knauer RS, Weitzman ED (1980) REM density is dissociated from REM sleep timing during free-running sleep episodes. Sleep 2:409–415

    PubMed  CAS  Google Scholar 

  108. Weitzman ED, Czeisler CA, Zimmermann JC, Ronda JM (1980) Timing of REM and stages 3 + 4 sleep during temporal isolation in man. Sleep 2:391–407

    PubMed  CAS  Google Scholar 

  109. Hiddinga AE, Beersma DGM, Van Den Hoofdakker RH (1997) Endogenous and exogenous components in the circadian variation of core body temperature in humans. J Sleep Res 6:156–163

    Article  PubMed  CAS  Google Scholar 

  110. Wyatt JK, Ritz-De Cecco A, Czeisler CA, Dijk DJ (1999) Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day. Am J Physiol Regul Integr Comp Physiol 277:R1152–R1163

    CAS  Google Scholar 

  111. Hull JT, Wright KP Jr, Czeisler CA (2003) The influence of subjective alertness and motivation on human performance independent of circadian and homeostatic regulation. J Biol Rhythms 18:329–338

    Article  PubMed  Google Scholar 

  112. Dijk DJ, Shanahan TL, Duffy JF, Ronda JM, Czeisler CA (1997) Variation of electroencephalographic activity during non-rapid eye movement and rapid eye movement sleep with phase of circadian melatonin rhythm in humans. J Physiol 505:851–858

    Article  PubMed  CAS  Google Scholar 

  113. Wyatt J, Dijk D, Ritz-De Cecco A, Ronda J, Czeisler C (2006) Sleep facilitating effect of exogenous melatonin in healthy young men and women is circadian-phase dependent. Sleep 29:609–610

    PubMed  Google Scholar 

  114. Cajochen C, Brunner DP, Kräuchi K, Graw P, Wirz-Justice A (2000) EEG and subjective sleepiness during extended wakefulness in seasonal affective disorder: circadian and homeostatic influences. Biol Psychol 47:610–617

    Article  CAS  Google Scholar 

  115. Steriade M, McCormick DA, Sejnowski TJ (1993) Thalamocortical oscillations in the sleeping and aroused brain. Science 262:679–685

    Article  PubMed  CAS  Google Scholar 

  116. Amzica F, Steriade M (1998) Electrophysiological correlates of sleep delta waves. Electroencephalogr Clin Neurophysiol 107:69–83

    Article  PubMed  CAS  Google Scholar 

  117. Siapas AG, Wilson MA (1998) Coordinated interactions between hippocampal ripples and cortical spindles during slow-wave sleep. Neuron 21:1123–1128

    Article  PubMed  CAS  Google Scholar 

  118. Schibler U (2005) The daily rhythms of genes, cells and organs. Biological clocks and circadian timing in cells. EMBO J 6:9–13

    Article  CAS  Google Scholar 

  119. Schibler U, Naef F (2005) Cellular oscillators: rhythmic gene expression and metabolism. Curr Opin Cell Biol 17:223–229

    Article  PubMed  CAS  Google Scholar 

  120. Ebisawa T, Uchiyama M, Kajimura N, Mishima K, Kamei Y, Katoh M, Watanabe T, Sekimoto M, Shibui K, Kim K, Kudo Y, Ozeki Y, Sugishita M, Toyoshima R, Inoue Y, Yamada N, Nagase T, Ozaki N, Ohara O, Ishida N, Okawa M, Takahashi K, Yamauchi T (2001) Association of structural polymorphisms in the human period 3 gene with delayed sleep phase syndrome. EMBO report 2:342–346

    Article  CAS  Google Scholar 

  121. Naylor E, Bergmann BM, Krauski K, Zee PC, Takahashi JS, Vitaterna MH, Turek FW (2000) The circadian clock mutation after sleep homeostasis in the mouse. J Neurosci 20:8138–8143

    PubMed  CAS  Google Scholar 

  122. Antoch M, Song E, Chang A, Vitaterna M, Zhao Y, Wilsbacher L, Sangoram A, King D, Pinto L, Takahashi J (1997) Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. Cell 89:655–667

    Article  PubMed  CAS  Google Scholar 

  123. Kopp C, Albrecht U, Zheng B, Tobler I (2002) Homeostatic sleep regulation is preserved in mPer1and mPer2 mutant mice. Eur J Neurosci 16:1099–1106

    Article  PubMed  Google Scholar 

  124. Franken P, Thomason R, Heller HC, O’Hara BF (2007) A non-circadian role for clock-genes in sleep homeostasis: a strain comparison. BMC Neurosci 8:87–97

    Article  PubMed  CAS  Google Scholar 

  125. Boivin DB, James FO, Wu A, Cho-Park F, Xiong H, Sun ZS (2003) Circadian clock genes oscillate in human peripheral blood mononuclear cells. Blood 102:4143–4145

    Article  PubMed  CAS  Google Scholar 

  126. Archer SN, Viola AU, Kyriakopoulou V, von Schantz M, Dijk D (2008) Inter-Individual differences in habitual sleep timing and entrained phase of endogenous circadian rhythms of BMAL1, PER2 and PER3 mRNA in human leucocytes. Sleep 5:608–617

    Google Scholar 

  127. Viola AU, Archer SN, James LM, Groeger JA, Lo JCY, Skene DJ, Von Schantz M, Dijk DJ (2007) PER3 polymorphism predicts sleep structure and waking performance. Curr Biol 17:613–618

    Article  PubMed  CAS  Google Scholar 

  128. Dijk DJ, Franken P (2005) Interaction of sleep homeostasis and circadian rhythmicity: Dependent or independent systems? In: Kryger MH, Roth T, Dement WC (eds) Principles and practice of sleep medicine, 4th edn. Elsevier, Philadelphia, pp 418–434

    Google Scholar 

  129. Mecacci L, Zani A (1983) Morningness-eveningness preferences and sleep-waking diary data of morning and evening types in student and worker samples. Ergonomics 26:1147–1153

    Article  PubMed  CAS  Google Scholar 

  130. Duffy JF, Dijk DJ, Hall E, Czeisler CA (1999) Relationship of endogenous circadian melatonin and temperature rhythms to self-reported preference for morning or evening activity in young and older people. J Invest Med 47:141–150

    CAS  Google Scholar 

  131. Mongrain V, Lavoie S, Selmaoui B, Paquet J, Dumont M (2004) Phase relationships between sleep – wake cycle and underlying circadian rhythms in morningness – eveningness. J Biol Rhythms 19:248–257

    Article  PubMed  Google Scholar 

  132. Dijk DJ, Lockley SW (2002) Integration of human sleep–wake regulation and circadian rhythmicity. J Appl Psysiol 92:852–862

    Google Scholar 

  133. Mongrain V, Carrier J, Dumont M (2004) Circadian and homeostatic sleep regulation in morningness-eveningness. J Sleep Res 15:162–166

    Article  Google Scholar 

  134. Mongrain V, Carrier J, Dumont M (2006) Difference in sleep regulation between morning and evening circadian types as indexed by antero-posterior analyses of the sleep EEG. Eur J Neurosci 23:497–504

    Article  PubMed  Google Scholar 

  135. Schmidt C, Collette F, Leclercq Y, Sterpenich V, Vandewalle G, Berthomier P, Berthomier C, Phillips C, Tinguely G, Darsaud A, Gais S, Schabus M, Desseilles M, Dang-Vu T.T, Salmon E, Balteau E, Dequeldre C, Luxen A, Maquet P, Cajochen C, Peigneux P (2009) Homeostatic sleep pressure and responses to sustained attention in the suprachiasmatic area. Science, 324(5926):516–519

    Google Scholar 

  136. Aeschbach D, Cajochen C, Landolt H, Borbély AA (1996) Homeostatic sleep regulation in habitual short sleepers and long sleepers. Am J Physiol Regul Integr Comp Physiol 270:R41–R53

    CAS  Google Scholar 

  137. Aeschbach D, Sher L, TT P (2003) A longer biological night in long sleepers than in short sleepers. Am J Physiol Endocrinol Metab 88:26–30

    CAS  Google Scholar 

  138. Buysse DJ, Browman KE, Monk TH, Reynolds CF III, Fasiczka AL, Kupfer DJ (1992) Napping and 24 – hour sleep/wake patterns in healthy elderly and young adults. J Am Geriatr Soc 40:779–786

    PubMed  CAS  Google Scholar 

  139. Bliwise DL (1993) Sleep in normal aging and dementia. Sleep 16:40–81

    PubMed  CAS  Google Scholar 

  140. Czeisler CA, Dumont M, Duffy JF, Steinberg JD, Richardson GS, Brown EN, Sànchez R, Rios CD, Ronda JM (1992) Association of sleep–wake habits in older people with changes in output of circadian pacemaker. Lancet 340:933–936

    Article  PubMed  CAS  Google Scholar 

  141. Duffy JF, Dijk DJ, Klerman BE, Czeisler CA (1998) Later endogenous circadian temperature nadir relative to an earlier wake time in older people. Am J Physiol Regul Integr Comp Physiol 275:R1478–R1487

    CAS  Google Scholar 

  142. Duffy JF, Czeisler CA (2002) Age-related change in the relationship between circadian period, circadian phase, and diurnal preference in humans. Neurosci Lett 318:117–120

    Article  PubMed  CAS  Google Scholar 

  143. Münch M, Knoblauch V, Blatter K, Schröder C, Schnitzler C, Kräuchi K, Wirz-Justice A, Cajochen C (2004) The frontal predominance in human EEG delta activity after sleep loss decreases with age. Eur J Neurosci 20:1402–1410

    Article  PubMed  Google Scholar 

  144. Dijk DJ, Duffy JF, Riel E, Shanahan TL, Czeisler CA (1999) Ageing and the circadian and homeostatic regulation of human sleep during forced desynchrony of rest, melatonin and temperature rhythms. J Physiol 516:611–627

    Article  PubMed  CAS  Google Scholar 

  145. Münch M, Knoblauch V, Blatter K, Schroder C, Schnitzler C, Krauchi K, Wirz-Justice A, Cajochen C (2005) Age-related attenuation of the evening circadian arousal signal in humans. Neurobiol Aging 26:1307–1319

    Article  PubMed  Google Scholar 

  146. Münch M, Knoblauch V, Blatter K, Wirz-Justice A, Cajochen C (2007) Is homeostatic sleep regulation under low sleep pressure modified by age? Sleep 30:781–792

    PubMed  Google Scholar 

  147. Wirz-Justice A (2003) Chronobiology and mood disorders. Dialogues Clin Neurosci 5:223–233

    Google Scholar 

  148. Van Someren EJW (2000) Circadian and sleep disturbances in the elderly. Exp Gerontol 35:1229–1237

    Article  PubMed  Google Scholar 

  149. Riemersma-van der Lek RF, Swaab DF, Twisk J, Hol EM, Hoogendijk WJG, Van Someren E (2008) Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities. JAMA 299:2642–2655

    Article  PubMed  CAS  Google Scholar 

  150. Van Someren EJW, Hagebeuk EEO, Lijzenga C, Scheltens P, De Rooij SEJA, Jonker C, Pot AM, Mirmiran M, Swaab DF (1996) Circadian rest-activity rhythm disturbances in Alzheimer’s disease. Biol Psychiatry 40:259–270

    Article  PubMed  Google Scholar 

  151. Wu YH, Swaab DF (2006) Disturbance and strategies for reactivation of the circadian rhythm system in aging and Alzheimer’s disease. Sleep Med 8:623–636

    Article  Google Scholar 

  152. Ferrari E, Arcaini A, Gornati R, Pelanconi L, Cravello L, Fioravanti M, Solerte SB, Magri F (2000) Pineal and pituitary-adrenocortical function in physiological aging and in senile dementia. Exp Gerontol 35:1239–1250

    Article  PubMed  CAS  Google Scholar 

  153. Perlis ML, Giles DE, Buysse DJ, Thase ME, Tu X, Kupfer DJ (1997) Which depressive symptoms are related to which sleep electroencephalographic variables? Biol Psychiatry 42:904–913

    Article  PubMed  CAS  Google Scholar 

  154. Riemann D, Berger M, Voderholzer U (2001) Sleep and depression – results from psychobiological studies: an overview. Biol Psychol 57:67–103

    Article  PubMed  CAS  Google Scholar 

  155. Boivin DB (2000) Influence of sleep–wake and circadian rhythm disturbances in psychiatric disorders. J Psychiatry Neurosci 25:446–458

    PubMed  CAS  Google Scholar 

  156. Lewy AJ, Lefler BJ, Emens JS, Bauer VK (2006) The circadian basis of winter depression. Proc Natl Acad Sci U S A 103:7414–7419

    Article  PubMed  CAS  Google Scholar 

  157. Chellappa SL, Araujo JF (2007) Sleep disorders and suicidal ideation in patients with depressive disorder. Psychiatr Res 153:131–136

    Article  Google Scholar 

  158. Chellappa SL, Araújo JF (2006) Excessive daytime sleepiness in patients with depressive disorder. Rev Bras Psiquiatr 28:126–130

    Article  PubMed  Google Scholar 

  159. Fava M (2004) Daytime sleepiness and Insomnia as correlates of depression. J Clin Psychiatry 65:27–32

    Article  PubMed  Google Scholar 

  160. Drennan MD, Klauber MR, Kripke DF, Goyette LM (1991) The effects of depression and age on the Horne–Ostberg morningness-eveningness score. J Affect Disord 23:93–98

    Article  PubMed  CAS  Google Scholar 

  161. Johansson C, Willeit M, Smedh C, Ekholm J, Paunio T, Kieseppä T, Lichtermann D, Praschak-Rieder N, Neumeister A, Nilsson LG, Kasper S, Peltonen L, Adolfsson R, Schalling M, Partonen T (2003) Circadian clock-related polymorphisms in seasonal affective disorder and their relevance to diurnal preference. Neuropsychopharmacology 28:734–739

    Article  PubMed  CAS  Google Scholar 

  162. Katzenberg D, Young T, Finn L, Lin L, King DP, Takahashi J (1998) A CLOCK polymorphism associated with human diurnal preference. Sleep 21:569–576

    PubMed  CAS  Google Scholar 

  163. McClung CA (2007) Circadian genes, rhythms and the biology of mood disorders. Pharmacol Thera 114:222–232

    Article  CAS  Google Scholar 

  164. Landolt HP, Raimo EB, Schnierow BJ, Kelsoe JR, Rapaport MH, Gillin JC (2001) Sleep and sleep electroencephalogram in depressed patients treated with phenelzine. Arch Gen Psychiatry 58:268–276

    Article  PubMed  CAS  Google Scholar 

  165. Cajochen C (2007) Alerting effects of light. Sleep Med Rev 11:453–464

    Article  PubMed  CAS  Google Scholar 

  166. Cajochen C, Wyatt JK, Bonikowska M, Czeisler C, Dijk DJ (2000) Non-linear interaction between circadian and homeostatic modulation of slow eye movements during wakefulness in humans. J Sleep Res 9(S1):29

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. The CAPES Foundation / Ministry of Education of Brazil, Brasilia, DF, Brazil

    Sarah Laxhmi Chellappa

  2. Centre for Chronobiology, Psychiatric University Clinics, Wilhelm Kleinstrasse 27, CH-4025, Basel, Switzerland

    Sarah Laxhmi Chellappa & Christian Cajochen

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  1. Sarah Laxhmi Chellappa
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Correspondence to Sarah Laxhmi Chellappa .

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    Urs Albrecht

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Chellappa, S.L., Cajochen, C. (2010). The Circadian Clock and the Homeostatic Hourglass: Two Timepieces Controlling Sleep and Wakefulness. In: Albrecht, U. (eds) The Circadian Clock. Protein Reviews, vol 12. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1262-6_9

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