Abstract
Many functional aspects of wakefulness and sleep, including excessive daytime sleepiness, vigilance, attention, sleep structure, and quantitative measures derived from the electroencephalogram (EEG) are tightly controlled by two interacting processes: (1) a circadian program providing temporal context to most physiological processes including sleep and (2) a homeostatic process keeping track of “sleep pressure.” Sleep homeostasis is conceptualized in the two-process model of sleep regulation [1] as the build-up of sleep pressure (or “sleep need”) during wakefulness and the dissipation of sleep pressure during sleep. The homeostatic regulation of rest/sleep is a common principle in invertebrates, fish, and mammals [2]. In humans, we think today that the circadian system opposes homeostatic changes in sleep pressure, to enable healthy people to stay awake and alert throughout a normal waking day despite accumulating sleep pressure associated with wakefulness [3]. Vice versa, circadian clock and sleep homeostasis interact to permit healthy individuals to remain asleep during the night despite the waning of sleep need. When wakefulness is prolonged (“sleep deprivation”) and sleep pressure exceeds an average “reference value,” subjective and objective measures of sleepiness increase, vigilance deteriorates, and attention is impaired. Moreover, theta activity in the waking EEG, as well as slow-wave sleep (SWS; nonREM sleep stages 3 and 4) and EEG slow-wave activity (SWA; spectral power within 0.75–4.5 Hz) are enhanced in recovery sleep. Particularly, SWA (or “delta activity”) in nonREM sleep is predictably correlated with the duration of preceding wakefulness. This physiological measure constitutes the classical, highly reliable marker of sleep homeostasis, which served to delineate the basic concepts of the two-process model of sleep regulation [1,4]. The neurobiological mechanisms underlying nonREM sleep homeostasis remain incompletely understood.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Borbély AA. A two process model of sleep regulation. Hum Neurobiol. 1982;1:195–204.
Cirelli C, Tononi G. Is sleep essential? PLoS Biol. 2008;6:1605–11.
Franken P, Dijk DJ. Circadian clock genes and sleep homeostasis. Eur J Neurosci. 2009;29:1820–9.
Daan S, Beersma DGM, Borbély AA. Timing of human sleep: recovery process gated by a circadian pacemaker. Am J Physiol. 1984;246:R161–78.
Basheer R, Strecker RE, Thakkar MM, McCarley RW. Adenosine and sleep-wake regulation. Prog Neurobiol. 2004;73:379–96.
Landolt HP. Sleep homeostasis: a role for adenosine in humans? Biochem Pharmacol. 2008;75:2070–9.
Haydon PG, Carmignoto G. Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev. 2006;86:1009–31.
Pascual O, Casper KB, Kubera C, et al. Astrocytic purinergic signaling coordinates synaptic networks. Science. 2005;310:113–6.
Halassa MM, Florian C, Fellin T, et al. Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron. 2009;61:213–9.
Fredholm BB, Chen JF, Cunha RA, Svenningsson P, Vaugeois JM. Adenosine and brain function. Internatl Rev Neurobiol. 2005;63:191–270.
Franken P, Chollet D, Tafti M. The homeostatic regulation of sleep need is under genetic control. J Neurosci. 2001;21:2610–21.
Rétey JV, Adam M, Honegger E, et al. A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans. Proc Natl Acad Sci U S A. 2005;102:15676–81.
Sebastiao AM, Ribeiro JA. Adenosine receptors and the central nervous system. In: Wilson CN, Mustafa SJ, editors. Handbook of experimental pharmacology, vol. 193. Berlin, Heidelberg: Springer; 2009. p. 471–534.
Bauer A, Ishiwata K. Adenosine receptor ligands and PET imaging of the CNS. In: Wilson CN, Mustafa SJ, editors. Handbook of experimental pharmacology, vol. 193. Berlin, Heidelberg: Springer; 2009. p. 617–42.
Stenberg D, Litonius E, Halldner L, Johansson B, Fredholm BB, Porkka-Heiskanen T. Sleep and its homeostatic regulation in mice lacking the adenosine A1 receptor. J Sleep Res. 2003;12:283–90.
Thakkar MM, Winston S, McCarley RW. A1 receptor and adenosinergic homeostatic regulation of sleep-wakefulness: effects of antisense to the A1 receptor in the cholinergic basal forebrain. J Neurosci. 2003;23:4278–87.
Bjorness TE, Kelly CL, Gao TS, Poffenberger V, Greene RW. Control and function of the homeostatic sleep response by adenosine A(1) receptors. J Neurosci. 2009;29:1267–76.
Elmenhorst D, Basheer R, McCarley RW, Bauer A. Sleep deprivation increases A(1) adenosine receptor density in the rat brain. Brain Res. 2009;1258:53–8.
Elmenhorst D, Meyer PT, Winz OH, et al. Sleep deprivation increases A(1) adenosine receptor binding in the human brain: A positron emission tomography study. J Neurosci. 2007;27:2410–5.
Scammell TE, Gerashchenko DY, Mochizuki T, et al. An adenosine A2a agonist increases sleep and induces Fos in ventrolateral preoptic neurons. Neuroscience. 2001;107:653–63.
Gallopin T, Luppi PH, Cauli B, et al. The endogenous somnogen adenosine excites a subset of sleep-promoting neurons via A2A receptors in the ventrolateral preoptic nucleus. Neuroscience. 2005;134:1377–90.
Hayaishi O, Urade Y, Eguchi N, Huang Z-L. Genes for prostaglandin D synthase and receptor as well as adenosine A2A receptor are involved in the homeostatic regulation of NREM sleep. Arch Ital Biol. 2004;142:533–9.
Huang ZL, Qu WM, Eguchi N, et al. Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat Neurosci. 2005;8:858–9.
Rétey JV, Adam M, Khatami R, et al. A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. Clin Pharmacol Ther. 2007;81:692–8.
Rétey JV, Adam M, Gottselig JM, et al. Adenosinergic mechanisms contribute to individual differences in sleep-deprivation induced changes in neurobehavioral function and brain rhythmic activity. J Neurosci. 2006;26:10472–9.
Landolt HP, Rétey JV, Tönz K, et al. Caffeine attenuates waking and sleep electroencephalographic markers of sleep homeostasis in humans. Neuropsychopharmacology. 2004;29:1933–9.
Wyatt JK, Cajochen C, Ritz-De Cecco A, Czeisler CA, Dijk DJ. Low-dose repeated caffeine administration for circadian-phase-dependent performance degradation during extended wakefulness. Sleep. 2004;27:374–81.
Khatami R, Landolt HP, Achermann P, et al. Insufficient non-REM sleep intensity in narcolepsy-cataplexy. Sleep. 2007;30:980–9.
Besset A, Tafti M, Nobile L, Billiard M. Homeostasis and narcolepsy. Sleep. 1994;17:S29–34.
Khatami R, Landolt HP, Achermann P, et al. Challenging sleep homeostasis in narcolepsy-cataplexy: implications for non-REM and REM sleep regulation. Sleep. 2008;31:859–67.
Olafsdottir BR, Rye DB, Scammell TE, Matheson JK, Stefansson K, Gulcher JR. Polymorphisms in hypocretin/orexin pathway genes and narcolepsy. Neurology. 2001;57:1896–9.
Dauvilliers Y, Baumann CB, Carlander B, et al. CSF hypocretin-1 levels in narcolepsy, Kleine-Levin syndrome, and other hypersomnias and neurological conditions. J Neurol Neurosurg Psychiatry. 2003;74:1667–73.
Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature. 2005;437:1257–63.
Mochizuki T, Crocker A, McCormack S, Yanagisawa M, Sakurai T, Scammell TE. Behavioral state instability in orexin knock-out mice. J Neurosci. 2004;24:6291–300.
Liu ZW, Gao XB. Adenosine inhibits activity of hypocretin/orexin neurons by the A1 receptor in the lateral hypothalamus: A possible sleep-promoting effect. J Neurophysiol. 2007;97:837–48.
Satoh S, Matsumura H, Kanbayashi T, et al. Expression pattern of FOS in orexin neurons during sleep induced by an adenosine A(2A) receptor agonist. Behav Brain Res. 2006;170:277–86.
Mitler MM, Walsleben J, Sangal RB, Hirshkowitz M. Sleep latency on the maintenance of wakefulness test (MWT) for 530 patients with narcolepsy while free of psychoactive drugs. Electroencephalogr Clin Neurophysiol. 1998;107:33–8.
Conlay LA, Conant JA, deBros F, Wurtman R. Caffeine alters plasma adenosine levels. Nature. 1997;389:136.
Siegel JM. Narcolepsy. Sci Am. 2000;282:76–81.
Acknowledgments
The author thanks Dr. Caroline Kopp for discussion and helpful comments on the manuscript. His research summarized in this chapter was supported by Swiss National Science Foundation, Center for Neuroscience Zürich (ZNZ), and Zürich Center for Integrative Human Physiology (ZIHP).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Landolt, HP. (2011). Sleep Homeostasis, Adenosine, Caffeine, and Narcolepsy. In: Baumann, C., Bassetti, C., Scammell, T. (eds) Narcolepsy. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-8390-9_8
Download citation
DOI: https://doi.org/10.1007/978-1-4419-8390-9_8
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-8389-3
Online ISBN: 978-1-4419-8390-9
eBook Packages: MedicineMedicine (R0)