Homeostatic regulation of sleep

Mathematical analyses of EEG SWA have yielded quantitative information about the time course of accumulation and discharge of sleep need. The dynamics of the sleep/wake-dependent changes in delta power have been quantified with the use of computer simulations, and delta power can now be predicted in detail. The increase of sleep need during waking can be described by an exponentially saturating curve with a time constant (Tj) of 18.2 hr in humans (37) and 8.6 hr in 

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Thakkar, M. M., Winston, S. McCarley, R. W. (2003b). Al receptor and adenosinergic homeostatic regulation of sleep-wakefulness effects of antisense to the Al receptor in the cholinergic basal forebrain. J. Neurosci. 23, 4278-87. 

Franken, P., Chollet, D. Tafti, M. (2001). The homeostatic regulation of sleep need is under genetic control. J. Neurosci 21 (8), 2610-21. 

As health professionals have become more aware of the importance of sleep, the treatment of sleep disorders has received increasing attention. As a result, new drugs have become available on the market and new information has become available on the role of sleep factors, the homeostatic regulation of sleep, circadian rhythm, chronotherapy, the role of immunology, and genetics of sleep disorders. The new knowledge will further enhance the ability of health professionalsto develop new medicines for the treatment of sleep disorders. 

Gvilia, I., Turner, A., McGinty, D Szymusiak, R. (2006). Preoptic area neurons and the homeostatic regulation of rapid eye movement sleep. J. Neurosci. 26, 3037-44. 

Strogatz, S. H., Kronauer, R. E. Czeisler, C. A (1986). Circadian regulation dominates homeostatic control of sleep length and prior wake length in humans. Sleep 9, 353-64. 

Hayaishi, O., et al. (2004). Genes for prostaglandin D synthase and receptor as well as adenosine A2A receptor are involved in the homeostatic regulation of mem sleep. Arch. Ital. Biol 142, 533-9. 

The second constellation of narcoleptic symptoms can be summarized under the rubric of excessive daytime sleepiness, or an inability to regulate wakefulness. As recently reviewed by Mochizuki et al. (2004), at least four explanations have to date been proposed for this sleepiness a deficit in arousal, an impaired circadian alertness signal, abnormal homeostatic regulation of non-REM sleep, and excessive vigilance state fragmentation. These mechanisms are not mutually exclusive, and there are possible roles for orexin signaling in each of them, as we review in the following sections. 

Dijk D, Duffy J, Riel E, Shanahan T, Czeisler C. Ageing and the circadian and homeostatic regulation of human sleep during forced desynchrony of rest, melatonin and temperature rhythms. Physiol 1999 516(2) 611—627. 

Boutrel, B Monaca, C., Hen, R., Hamon, M. Adrien, J. (2002). Involvement of 5-HTia receptors in homeostatic and stress-induced adaptive regulations of paradoxical sleep studies in 5-HT1A knock-out mice. J. Neurosci. 22, 4686-92. 

Because melatonin is sold over the counter and its production is not the subject of strict regulation as is that of prescribed medications, it is in wide use, but insufficient scientifically controlled information is available. Another consequence of the popularity and availability of the hormone is its use in a wide array of situations in which its efficacy has not been proven yet for instance, as treatment for neurodegenerative diseases or as a sleep-inducing medication. It also has been tried as an antidepressant, but that effect is still unclear. The administration of melatonin to patients with bipolar depression, especially to rapid cyclers, is of interest, especially if its use is associated with the presumed decrease in nocturnal hormonal levels and increase in sensitivity to light (Lewy et al. 1985). The possibility that melatonin also serves as a stabilizer of rhythm in these patients is in accord with the homeostatic effect of several other hormones that have been previously discussed here. 

Changes in performance capability during continuous wakefulness can be conceptualized as a two-process interaction (33), derived from the two-process model of sleep regulation (54). Specifically, sleepiness and performance are influenced by the homeostatic sleep drive (producing monotonic increases in impairment) and by circadian rhythmicity (near 24-hr cycles) (33,58). Daily circadian modulation of neurocognitive performance has been consistently noted since the first studies of sleep deprivation and human performance (2,13). 

Dinges DF. Homeostatic and circadian regulation of wakefulness during jet lag and sleep deprivation effect of wake-promoting countermeasures. AFOSR Technical Report No. 31-08-2000. Arlington, VA Air Force Office of Scientific Research. 2000. 

Figure 2 Several models have been proposed to conceptualize the interaction of circadian and homeostatic processes in sleep regulation. In the two-process model, a sleep homeostatic process increases during waking and decreases during sleep ( Process S ) and interacts with input from the circadian system that is independent of sleep and waking ( Process C ) to gate the occurrence of sleep and wakefulness. (Adapted from Ref. 1.)...

One of the distinctive features of TMN neurons is that they contain high levels of adenosine deaminase, a key enzyme involved in deamination of adenosine, a mediator of homeostatic sleep regulation (Thakkar et al, 2003a, b). 

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