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PLoS Biol. Aug 2008; 6(8): e216.
Published online Aug 26, 2008. doi:  10.1371/journal.pbio.0060216
PMCID: PMC2525690

Is Sleep Essential?

Everybody knows that sleep is important, yet the function of sleep seems like the mythological phoenix: “Che vi sia ciascun lo dice, dove sia nessun lo sa” (“that there is one they all say, where it may be no one knows,” Wolfgang Amadeus Mozart and Lorenzo da Ponte [1790], Così fan tutte). But what if the search for an essential function of sleep is misguided? What if sleep is not required but rather a kind of extreme indolence that animals indulge in when they have no more pressing needs, such as eating or reproducing? In many circumstances sleeping may be a less dangerous choice than roaming around, wasting energy and exposing oneself to predators. Also, if sleep is just one out of a repertoire of available behaviors that is useful without being essential, it is easier to explain why sleep duration varies so much across species [1–4]. This “null hypothesis” [5–7] would explain why nobody has yet identified a core function of sleep. But how strong is the evidence supporting it? And are there counterexamples?

Sleep Function: The Null Hypothesis

So far the null hypothesis has survived better than alternatives positing some core function for sleep [8–10]. In what follows we shall test the null hypothesis by considering three of its key corollaries. If the null hypothesis were right, we would expect to find: (1) animals that do not sleep at all; (2) animals that do not need recovery sleep when they stay awake longer; and, finally, (3) that lack of sleep occurs without serious consequences.

Corollary 1: Are There Animals That Do Not Sleep?

Sleep is a reversible condition of reduced responsiveness usually associated with immobility. The decreased ability to react to stimuli distinguishes sleep from quiet wakefulness, while its reversibility distinguishes sleep from coma. Only a small number of species—mostly mammals and birds—have been evaluated in detail with respect to sleep. Most studies found signs of sleep, both behavioral (quiescence and hyporesponsivity) and electrophysiological (e.g., the slow waves of non-rapid eye movement [NREM] sleep). Scientists have been hesitant to attribute sleep to reptiles, amphibians, fish, and especially invertebrates, preferring the noncommittal term “rest” in the absence of electrophysiological signs resembling those of mammals and birds. Studies with Drosophila melanogaster [11,12], however, demonstrated that flies, also, become less responsive, i.e., sleep, when they remain quiescent for a few minutes. Moreover, sleep pressure increases if flies are kept awake, their sleep patterns change with the life span, and they are sensitive to hypnotics and stimulants [13–15]. Finally, the fly brain undergoes changes in gene expression between sleep and wakefulness similar to those observed in mammals [16,17], and shows changes in brain electrical activity [18]. Similar criteria have now been provided for zebrafish [19–21], and there is evidence that even the worm C. elegans shows a sleep-like state at a certain stage of development [22].

It has been argued that the assumption that sleep is universal is based on poor evidence [7]. Figure 1 summarizes some of the “difficult” cases. The bullfrog is often promoted as an example of an animal that does not sleep. There is, however, only one study on this topic, published in 1967 [23]. This report concluded that bullfrogs do not sleep because even during the resting phase they never failed to show a change in respiratory responses after painful stimuli (cutaneous shock). The same report acknowledged that arousal thresholds could not be measured during the cyclic phases with the lowest respiratory activity, nor could they be tested with other physiological stimuli, such as light or sound. Also, the underlying assumption in that study was that shocks delivered late at night (presumably in the middle of sleep) should elicit less respiratory response than those given early in the night (when sleep had just started); however, the opposite was found [23]. In fact, we now know that in rodents and humans the deepest sleep occurs early after sleep onset. At the very least, it seems that more experiments are needed before concluding that bullfrogs do not sleep.

Figure 1
Animal Species in Which the Presence of Sleep and/or Its Homeostatic Regulation Have Been Called into Question

Coral reef teleosts showing sleep swimming have similarly been used as evidence that not all animals sleep (Figure 1). Two types of reef fish have been studied in terms of sleep; one is immobile at night and less responsive to alerting stimuli (stationary sleep [24]), and another [25] retreats to the coral at night, where it continues to move its fins even when holding a fixed position (called “sleep swimming”; possibly to avoid hypoxia [25]). The researchers who studied these teleosts defined sleep swimming as a state “equivalent to sleep.” They assumed that sensory information must still be processed to a certain extent during sleep swimming, because each individual remains in its swimming zone during the night. Yet, the fish at night loses the ability to respond to predators [25], and mortality due to predators' attacks is much higher at night, when the fish is sheltering in corals, than during the day, when it feeds in open waters [26]. Most losses to predators occur in the first 1–2 h after sunset, i.e., at the beginning of the “rest” period. Although limited, the available evidence seems to suggest that sleep swimming is associated with hyporesponsivity.

In dolphins the very presence of sleep has been called into question because these marine mammals move continuously and their arousal thresholds have not been measured directly (Figure 2). Yet, dolphins are capable of engaging in slow waves with half of the brain at a time, a property called “unihemispheric sleep” [27–31]. Moreover, there is some limited evidence of decreased response to stimuli during stereotypical circular swimming, which is associated with unihemispheric sleep (Figure 2). The very fact that dolphins have developed the remarkable specialization that is unihemispheric sleep, rather than merely getting rid of sleep altogether, should count as evidence that sleep must serve some essential function and cannot be eliminated. Thus, there is no clear evidence of a species that does not sleep.

Figure 2
Sleep in Dolphins: A Difficult Case?

Corollary 2: Can Sleep Loss Occur without a Compensatory Rebound?

Are there animals in which sleep is not homeostatically regulated? Cockroaches, honeybees, and tilapia (Figure 1) are seen as species lacking this mechanism, because their response to sleep deprivation does not consistently include an increase in sleep time. However, it is well known that sleep has both a quantitative (duration) and a qualitative (intensity) dimension [32,33]. Sleep can be recovered by sleeping longer, more deeply (for instance in mammals NREM sleep becomes richer in slow waves), and/or in a more consolidated manner (sleep is less frequently interrupted by brief awakenings). Claims that in some animals sleep is not homeostatically regulated should be made only after several aspects of the response to sleep loss have been analyzed, including changes in sleep intensity and pattern.

Evidence of apparent lack of sleep rebound comes from an early study of sleep deprivation using constant light in the pigeon [34], in which sleep was nearly eliminated in the birds for more than 10 d, with no subsequent increases in either total sleep time or slow-wave activity (SWA). Considered one of the best markers of sleep intensity, SWA is a measure of the number and amplitude of slow waves during NREM sleep [35]. However, in this study the overall amount of SWA was preserved across the entire sleep deprivation period in constant light, suggesting that the increasing sleep pressure may have forced sleep slow waves to leak into wakefulness.

There is evidence that zebrafish sleep and show sleep rebound after sleep is prevented by electrical or mechanical stimulation but not by light exposure, which can drastically reduce sleep for several days [19–21]. We interpret these findings to mean that light is a powerful arousing stimulus in zebrafish, not that sleep in this animal is dispensable. Even with light exposure, 15%–20% of baseline sleep remains, and this percentage increases if constant light is maintained for more than one week [21]. Moreover, it is unknown whether in zebrafish prolonged light exposure affects sleep intensity or causes long-term detrimental effects.

In the dolphin, not only the existence of sleep itself, but sleep homeostasis has been questioned also. The single published study on this issue, however, clearly shows that unihemispheric sleep is homeostatically regulated (Figure 2).

By reviewing the data used to support the claim that sleep is not universal [7], we instead reach the opposite conclusion: sleep is present and strictly regulated in all animal species that have been carefully studied so far.

Corollary 3: Can Sleep Loss Occur without Negative Consequences?

Harmful consequences of sleep deprivation have been described in many studies. Most dramatically, prolonged sleep deprivation leads to death. Rats kept awake using the disk-over-water method develop a peripheral syndrome characterized by increased metabolic rate and decreased body weight, which culminates in death after 2–4 wk [36]. Prolonged sleep deprivation is also fatal in flies [37], cockroaches [38], and humans with fatal familial insomnia, who die after developing a syndrome not unlike that seen in sleep-deprived rats [39]. Pigeons, however, appear capable of surviving prolonged sleep deprivation [40]. Prolonged sleep deprivation has not been studied in other species. Thus, it is unclear whether death, when it occurs, is due to loss of sleep per se or to other factors, such as forced arousals and the associated stress.

Sleep intrusion.

Whether or not sleep loss is lethal, sleep deprivation has two consequences that never fail to occur (but see Figure 2). The first one is intrusion of sleep into wakefulness. When wakefulness is enforced, sleep pressure increases and sleep cannot be avoided, irrespective of stimulation. During short-term (6–24 h) sleep deprivation experiments, some portion of baseline sleep (usually 5%–10%) is always maintained (e.g., flies [15], zebrafish [21], mice [41], rats [42], rabbits [43], hamsters [44], and dolphins [45]). Under a chronic “total” sleep deprivation regimen, rats still sleep at least 10% of the time, due to “microsleep” episodes [36]. Perhaps even more important, spectral analysis of the electroencephalogram (EEG) reveals that slower EEG activity (delta, < 4 Hz; or theta, 4–7 Hz) leaks into periods during which the animal may be moving around with eyes open, and which are therefore conventionally scored as wakefulness [42,46].

It is easier to keep humans awake. Especially motivated subjects can be kept awake for up to several days (for 11 d in the famous case of Randy Gardner [47]) by keeping busy with pleasurable activities. (Although seriously sleep deprived humans have been reported to fall asleep even in the most dangerous situations [48].) People may seem superficially awake (moving and with eyes open) even though the EEG slows down or exhibits microsleeps [49,50]. Few studies so far have investigated the leakage of slower brain activity in the EEG of sleep deprived humans, though several studies show an increase in power in the theta frequency bands with prolonged wakefulness and sleep deprivation [50,51].

It is unknown whether the presence of slower activity in the “wake” EEG spectra of sleep-deprived animals or humans is due to “piecemeal” sleep, where some brain regions may be asleep whereas others are awake [52], to “salt and pepper” sleep-wake, in which within the same brain regions individual neurons may be awake (depolarized) and others may be oscillating between up- and downstates (asleep, [53]), or to abnormal cellular activity that is neither wake or sleep. Whatever the underlying cellular events, it seems impossible to completely deprive an animal of sleep for more than 24 h [54]. Rather, what seems to occur is a kind of “dormiveglia” (sleepwake), a mixed state that is clearly dysfunctional.

Cognitive impairment.

The second documented consequence of sleep deprivation is performance deterioration, especially cognitive impairment. Intriguingly, there is great inter-individual variability in the susceptibility of humans to the effects of sleep deprivation, and subjects whose performance is little impaired by one task may show great impairment in another task [55,56]. Partial sleep restriction also impairs cognitive performance, although subjects may not realize that they are impaired [57,58]. Cognitive impairment is easier to study in humans than in animals, but there is now evidence that both acute sleep loss and sleep restriction affect cognitive function in flies [59], birds [60], and rodents (e.g., [61]).

Sleepy or tired?

An important unsolved question is whether the impairment, cognitive or otherwise, that follows sleep deprivation is merely the consequence of an increased drive for sleep (“sleepiness”) or whether brain cells need sleep because they are actually “tired.” Pure sleepiness can be conceptualized as the effect of central sleep-promoting mechanisms telling the brain it is time to sleep, whether or not brain cells need to do so. For instance, when we are jet-lagged, the circadian system may at times dampen the activity of arousal systems and boost that of sleep-promoting systems in brainstem, hypothalamus, and basal forebrain [62], even though we may not have been awake for long and presumably do not need extra sleep. Attention lapses or unresponsiveness in such circumstances could be due to the activation of sleep-promoting mechanisms, not to the brain being actually “tired.” Similar considerations apply to the increased sleepiness that follows a heavy meal, the use of sedatives, a boring environment, and so on.

Conversely, it may be that brain cells actually do get tired as a function of waking activities, whether or not the arousal systems are pushing the organism to stay awake. This may be the case, for instance, when we try to prolong wakefulness using amphetamines or other arousal-promoting drugs: though we are alert, certain aspects of performance seem to deteriorate [63]. Pure tiredness can be conceptualized as the inability of brain cells to continue functioning in their normal waking mode, despite the central wake-promoting mechanisms telling the brain it should be fully alert. PET studies show that glucose metabolism decreases more in prefrontal and parietal association areas involved in attention, judgment, and associative functions than in primary sensory and motor areas [64–67]. These results are more consistent with some parts of the brain being disproportionately “tired” than with the entire brain being “sleepy.”

Altogether, then, while we still do not understand whether sleep deprivation is followed by sleep intrusions and cognitive impairment because we become sleepy, tired, or both, the evidence so far indicates that, contrary to the predictions of the null hypothesis, lack of sleep has serious consequences, especially for the brain.

Sleep Function: Beyond the Null Hypothesis

The three corollaries of the null hypothesis do not seem to square well with the available evidence: there is no convincing case of a species that does not sleep, no clear instance of an animal that forgoes sleep without some compensatory mechanism, and no indication that one can truly go without sleep without paying a high price. What many concluded long ago still seems to hold: the case is strong for sleep serving one or more essential functions [9,10]. But which ones? The points below represent judgment calls that may be helpful in provoking discussions, guiding hypotheses and, above all, inspiring experimental tests.

A universal function.

It may still be wise to search for a function or functions that apply to all animals. It is unknown whether a proto-sleep state emerged early in evolution, perhaps out of the rest–activity cycle, or whether sleep emerged multiple times in the course of evolution. In either case, the simplest hypothesis (after the null hypothesis) is that sleep evolved to serve the same function in all species.

A core function.

There is no doubt that sleep, by changing so many aspects of physiology and behavior, affects the vast majority of body functions, from immunity to hormonal regulation to metabolism to thermoregulation. However, the simplest hypothesis (after the null hypothesis) is that there may be a single core function that requires sleep, and adventitious functions that take advantage of sleep.

A function transcending specific phenotypes and mechanisms.

Sleep comes in many forms. In the best known example, brain activity in NREM sleep and REM sleep is remarkably different: the EEG of NREM sleep is distinctive, with slow waves and spindles, and the EEG of REM is similar to that of wakefulness [68]. Brain metabolism is low in NREM sleep but high in REM sleep [69]. Thermoregulation is preserved in NREM sleep but not in REM sleep [70]. It is therefore assumed that these two phases of sleep perform quite different functions. It is highly unlikely that fly brains can produce slow waves or spindles [18], and they do not seem to have the equivalent of REM sleep. The mechanisms of sleep can also vary considerably: the hypocretin–orexin system has an arousing action in mammals but may have a hypnogenic effect in zebrafish [21]. It may be, of course, that each variation in sleep phenotype or mechanism implies a different function (and to some extent functional differences must exist), but it is perhaps more parsimonious to assume that there may be many ways to achieve the same goal. After all, in NREM as in REM stages, in fruit flies as in zebrafish as in humans, the organism (or parts of it) is quiescent and unresponsive—that is, asleep.

A neural function.

Although the entire body benefits from sleep [71], the most immediate, unavoidable effect of sleep deprivation is cognitive impairment. The brain suffers most from sleep deprivation. It is less clear that the rest of the body suffers as rapidly, significantly, or inevitably from lack of sleep. Although we talk about a muscle that is active or at rest, muscle rest can be achieved during quiet wakefulness, and does not seem to require sleep. However, few studies have compared directly the restorative value of quiet wakefulness and sleep for either the brain or any other organ [48,72]. This is a research approach that clearly deserves more emphasis in the future.

A cellular function.

If sleep has a core function involving the brain, such a function might be identifiable at the cellular level and there would be a price for brain cells to remain indefinitely awake. Indeed, the search for the function of sleep has often focused on identifying neuronal resources depleted during wakefulness and restored during sleep or, alternatively, neurotoxic substances that accumulate during wakefulness and dissipate during sleep. In mice, sleep may favor the replenishment of glycogen in glial stores [73], but this may be the case in only a few brain regions, and not in all mouse strains [74,75]. It has also been proposed that sleep may allow the removal of toxic free radicals accumulated in the brain during wakefulness [76,77]. However, studies in long-term sleep deprived rats found evidence for oxidative stress, but not oxidative damage (e.g., [78,79]). This result suggests that the cellular stress response induced during wakefulness may be sufficient to avoid long-term negative effects [80,81]. Other possibilities that are worth exploring are inspired by the recent systematic data on changes in brain gene expression that occur between sleep and wakefulness or after sleep deprivation [16,17,80,82–89]. In all species studied (flies, mice, rats, hamsters, and sparrows), wakefulness leads to the up-regulation of three categories of transcripts—those involved in energy metabolism, in the response to cellular stress, and in activity-dependent processes of synaptic potentiation. By contrast, transcripts expressed at higher levels during sleep are involved in synaptic depression and depotentiation, in the synthesis/maintenance of membranes, and in lipid metabolism [80,87]. One way to make sense of these apparently disparate findings is in terms of plastic processes. For example, we have suggested that during wakefulness, when animals interact with the environment and need to learn, there is a net increase in synaptic strength in many brain areas, in which case sleep would be needed to renormalize such changes [90,91]. A net increase of synaptic strength at the end of a waking day would result in higher energy consumption [92,93], larger synapses that take up precious space [94], and saturation of the capacity to learn. Also, a net strengthening of synapses likely represents a major source of cellular stress [80–82], due to the need to synthesize and deliver cellular constituents ranging from mitochondria to synaptic vesicles to various proteins and lipids. In this view, then, sleep would be necessary to renormalize synapses to a baseline level that is sustainable and ensures cellular homeostasis.

A function that cannot be provided by quiet wakefulness and that benefits from environmental disconnection.

If wakefulness were as good as sleep in fulfilling a fundamental biological function (or even nearly as good), is it likely that sleep would be so ubiquitous? Why would an animal choose to spend long periods of time not just immobile, but above all disconnected from the environment? It would seem that, if sleep has a core function, and if this function is for the brain, it should be one the brain cannot fulfill during wakefulness, and one that benefits from being performed off-line. Among several options, those related to plasticity and memory are especially intriguing, not least since during sleep, despite the functional disconnection from the environment, most neurons remain spontaneously active at levels similar to wakefulness [95].

Off-line activity may be necessary to stimulate synapses that remain underused during the waking day [96–98], so they can be ready when their turn comes. It may also be an excellent way of maintaining old memories by keeping them “exercised,” or of weakening nonadaptive memory traces while strengthening the adaptive ones [99]. A related idea is that an offline activation of neural circuits may be especially important during development [100], perhaps to rehearse innate behavioral patterns [101]. And perhaps sleep may even favor the formation of new synaptic contacts to refresh the repertoire of circuits available for the selection and acquisition of new memories [102].

Alternatively, sleep may be a good time for consolidating and integrating new memories without interference from ongoing activities, and indeed human studies have provided evidence for sleep-dependent memory consolidation, at least in some tasks [103,104]. Consolidation may happen, for instance, by further strengthening synapses already potentiated during wakefulness [103,105,106]. The observation that neural circuits activated during learning are “reactivated” during sleep is consistent with this possibility (e.g., [107–111]). Another possibility is that signal-to-noise ratios may increase through the generalized downscaling of synapses, as synapses mediating firing patterns predictive of postsynaptic activation would “survive” better than random ones [90,91,112]. This scenario would prevent runaway synaptic potentiation and the saturation of the ability to learn. Moreover, it would dovetail nicely with the cellular need for synaptic homeostasis: renormalizing synapses during sleep would counteract the cellular stress brought about by synaptic potentiation during wakefulness.

Conclusion

While there is still no consensus on why animals need to sleep, it would seem that searching for a core function of sleep, particularly at the cellular level, remains a worthwhile exercise. Especially if, as argued here, sleep is universal, tightly regulated, and cannot be eliminated without deleterious consequences. In the end, the burden of proof rests with those who are attempting not only to reject the null hypothesis, but to gather positive evidence for the elusive phoenix of sleep.

Acknowledgments

We thank Drs. Ugo Faraguna, Stephanie Maret, and Irene Tobler for helpful comments, and Drs. Irene Tobler and Emmanuel Mignot for providing some of the pictures shown in Figure 1.

Glossary

Abbreviations

EEG
electroencephalogram
NREM
non-rapid eye movement
SWA
slow-wave activity

Footnotes

Chiara Cirelli and Giulio Tononi are in the Department of Psychiatry, University of Wisconsin, Madison, Wisconsin, United States of America.

Funding. This work was supported by the National Institute of Mental Health Grant P20 MH077967 (CC and GT), R01 GM 075315 to CC, and the National Institutes of Health Director's Pioneer award (GT), and R01 NS 055185 (GT).

References

  • Zepelin H, Rechtschaffen A. Mammalian sleep, longevity, and energy metabolism. Brain Behav Evol. 1974;10:425–470. [PubMed]
  • Campbell SS, Tobler I. Animal sleep: a review of sleep duration across phylogeny. Neurosci Biobehav Rev. 1984;8:269–300. [PubMed]
  • Lesku JA, Roth TC, Rattenborg NC, Amlaner CJ, Lima SL. Phylogenetics and the correlates of mammalian sleep: A reappraisal. Sleep Med Rev. 2008;12:229–244. [PubMed]
  • Capellini I, Barton RA, McNamara P, Preston BT, Nunn CL. Phylogenetic analysis of the ecology and evolution of mammalian sleep. Evolution. 2008. E-pub ahead of print. doi: 10.1111/j.1558-5646.2008.00392.x. [PMC free article] [PubMed]
  • Meddis R. On the function of sleep. Anim Behav. 1975;23:676–691. [PubMed]
  • Rial RV, Nicolau MC, Gamundi A, Akaarir M, Aparicio S, et al. The trivial function of sleep. Sleep Med Rev. 2007;11:311–325. [PubMed]
  • Siegel JM. Do all animals sleep. Trends Neurosci. 2008;31:208–213. [PubMed]
  • Horne JA. Sleep function, with particular reference to sleep deprivation. Ann CLin Res. 1985;17:199–208. [PubMed]
  • Rechtschaffen A. Current perspectives on the function of sleep. Perspect Biol Med. 1998;41:359–390. [PubMed]
  • Mignot E. Why we sleep: the temporal organization of recovery. PLoS Biol. 2008;6:e106. doi: 10.1371/journal.pbio.0060106. [PMC free article] [PubMed]
  • Hendricks JC, Finn SM, Panckeri KA, Chavkin J, Williams JA, et al. Rest in Drosophila is a sleep-like state. Neuron. 2000;25:129–138. [PubMed]
  • Shaw PJ, Cirelli C, Greenspan RJ, Tononi G. Correlates of sleep and waking in Drosophila melanogaster. Science. 2000;287:1834–1837. [PubMed]
  • Cirelli C. Searching for sleep mutants of Drosophila melanogaster. Bioessays. 2003;25:940–949. [PubMed]
  • Shaw P. Awakening to the behavioral analysis of sleep in Drosophila. J Biol Rhythms. 2003;18:4–11. [PubMed]
  • Ho KS, Sehgal A. Drosophila melanogaster: An insect model for fundamental studies of sleep. Methods Enzymol. 2005;393:772–793. [PubMed]
  • Cirelli C, LaVaute TM, Tononi G. Sleep and wakefulness modulate gene expression in Drosophila. J Neurochem. 2005;94:1411–1419. [PubMed]
  • Zimmerman JE, Rizzo W, Shockley KR, Raizen DM, Naidoo N, et al. Multiple mechanisms limit the duration of wakefulness in Drosophila brain. Physiol Genomics. 2006;27:337–350. [PubMed]
  • Nitz DA, van Swinderen B, Tononi G, Greenspan RJ. Electrophysiological correlates of rest and activity in Drosophila melanogaster. Curr Biol. 2002;12:1934–1940. [PubMed]
  • Zhdanova IV, Wang SY, Leclair OU, Danilova NP. Melatonin promotes sleep-like state in zebrafish. Brain Res. 2001;903:263–268. [PubMed]
  • Prober DA, Rihel J, Onah AA, Sung RJ, Schier AF. Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish. J Neurosci. 2006;26:13400–13410. [PubMed]
  • Yokogawa T, Marin W, Faraco J, Pezeron G, Appelbaum L, et al. Characterization of sleep in zebrafish and insomnia in hypocretin receptor mutants. PLoS Biol. 2007;5:e277. doi: 10.1371/journal.pbio.0050277. [PMC free article] [PubMed]
  • Raizen DM, Zimmerman JE, Maycock MH, Ta UD, You YJ, et al. Lethargus is a Caenorhabditis elegans sleep-like state. Nature. 2008;451:569–572. [PubMed]
  • Hobson JA. Electrographic correlates of behavior in the frog with special reference to sleep. Electroencephalogr Clin Neurophysiol. 1967;22:113–121. [PubMed]
  • Tauber ES, Weitzman ED. Eye movements during behavioral inactivity in certain Bermuda reef fish. Commun Behav Biol. 1969;3:131–135.
  • Goldshmid R, Holzman R, Weihs D, Genin A. Aeration of corals by sleep-swimming fish. Limnol Oceanogr. 2004;49:1832–1839.
  • Holbrook SJ, Schmitt RJ. Competition for shelter space causes density-dependent predation mortality in damselfishes. Ecology. 2002;83:2855–2868.
  • Mukhametov LM, Supin AY, Polyakova IG. Interhemispheric asymmetry of the electroencephalographic sleep patterns in dolphins. Brain Res. 1977;134:581–584. [PubMed]
  • Mukhametov LM. Unihemispheric slow-wave sleep in the Amazonian dolphin, Inia geoffrensis. Neurosci Lett. 1987;79:128–132. [PubMed]
  • Ridgway SH. Asymmetry and symmetry in brain waves from dolphin left and right hemispheres: some observations after anesthesia, during quiescent hanging behavior, and during visual obstruction. Brain Behav Evol. 2002;60:265–274. [PubMed]
  • Lyamin OI, Mukhametov LM, Chetyrbok IS, Vassiliev AV. Sleep and wakefulness in the southern sea lion. Behav Brain Res. 2002;128:129–138. [PubMed]
  • Lyamin OI, Mukhametov LM, Siegel JM, Nazarenko EA, Polyakova IG, et al. Unihemispheric slow wave sleep and the state of the eyes in a white whale. Behav Brain Res. 2002;129:125–129. [PubMed]
  • Tobler I. Is sleep fundamentally different between mammalian species. Behav Brain Res. 1995;69:35–41. [PubMed]
  • Tobler I. Phylogeny of sleep regulation. In: Kryger MH, Roth T, Dement WC, . Principles and practice of sleep medicine. 4th edition. Philadelphia: Elsevier Saunders; 2005. pp. 77–90. editors.
  • Berger RJ, Phillips NH. Constant light suppresses sleep and circadian rhythms in pigeons without consequent sleep rebound in darkness. Am J Physiol. 1994;267:R945–952. [PubMed]
  • Achermann P, Borbely AA. Mathematical models of sleep regulation. Front Biosci. 2003;8:S683–693. [PubMed]
  • Rechtschaffen A, Bergmann BM. Sleep deprivation in the rat: an update of the 1989 paper. Sleep. 2002;25:18–24. [PubMed]
  • Shaw PJ, Tononi G, Greenspan RJ, Robinson DF. Stress response genes protect against lethal effects of sleep deprivation in Drosophila. Nature. 2002;417:287–291. [PubMed]
  • Stephenson R, Chu KM, Lee J. Prolonged deprivation of sleep-like rest raises metabolic rate in the Pacific beetle cockroach, Diploptera punctata (Eschscholtz) J Exp Biol. 2007;210:2540–2547. [PubMed]
  • Montagna P, Lugaresi E. Agrypnia excitata: a generalized overactivity syndrome and a useful concept in the neurophysiopathology of sleep. Clin Neurophysiol. 2002;113:552–560. [PubMed]
  • Newman SM, Paletz EM, Rattenborg NC, Obermeyer WH, Benca RM. Sleep deprivation in the pigeon using the disk-over-water method. Physiol Behav. 2008;93:50–58. [PubMed]
  • Franken P, Malafosse A, Tafti M. Genetic determinants of sleep regulation in inbred mice. Sleep. 1999;22:155–169. [PubMed]
  • Franken P, Dijk D, Tobler I, Borbely A. Sleep deprivation in the rat: effects of electroencephalogram power spectra, vigilance states, and cortical temperature. Am J Physiol. 1991;261:R198–208. [PubMed]
  • Tobler I, Franken P, Scherschlicht R. Sleep and EEG spectra in the rabbit under baseline conditions and following sleep deprivation. Physiol Behav. 1990;48:121–129. [PubMed]
  • Larkin JE, Yokogawa T, Heller HC, Franken P, Ruby NF. Homeostatic regulation of sleep in arrhythmic Siberian hamsters. Am J Physiol Regul Integr Comp Physiol. 2004;287:R104–111. [PubMed]
  • Oleksenko AI, Mukhametov LM, Polyakova IG, Supin AY, Kovalzon VM. Unihemispheric sleep deprivation in bottlenose dolphins. J Sleep Res. 1992;1:40–44. [PubMed]
  • Friedman L, Bergmann BM, Rechtschaffen A. Effects of sleep deprivation on sleepiness, sleep intensity, and subsequent sleep in the rat. Sleep. 1979;1:369–391. [PubMed]
  • Gulevich G, Dement W, Johnson L. Psychiatric and EEG observations on a case of prolonged (264 hours) wakefulness. Arch Gen Psychiatry. 1966;15:29–35. [PubMed]
  • Rogers NL, Dorrian J, Dinges DF. Sleep, waking and neurobehavioural performance. Front Biosci. 2003;8:s1056–1067. [PubMed]
  • Naitoh P, Kales A, Kollar EJ, Smith JC, Jacobson A. Electroencephalographic activity after prolonged sleep loss. Electroencephalogr Clin Neurophysiol. 1969;27:2–11. [PubMed]
  • Cajochen C, Khalsa SB, Wyatt JK, Czeisler CA, Dijk DJ. EEG and ocular correlates of circadian melatonin phase and human performance decrements during sleep loss. Am J Physiol. 1999;277:R640–649. [PubMed]
  • Cajochen C, Wyatt JK, Czeisler CA, Dijk DJ. Separation of circadian and wake duration-dependent modulation of EEG activation during wakefulness. Neuroscience. 2002;114:1047–1060. [PubMed]
  • Pigarev IN, Nothdurft HC, Kastner S. Evidence for asynchronous development of sleep in cortical areas. Neuroreport. 1997;8:2557–2560. [PubMed]
  • Rector DM, Topchiy IA, Carter KM, Rojas MJ. Local functional state differences between rat cortical columns. Brain Res. 2005;1047:45–55. [PubMed]
  • Cirelli C, Tononi G. Total sleep deprivation. In: Kushida CA, editor. Sleep deprivation: basic science, physiology, and behavior. New York, NY: Marcel Dekker; 2005. pp. 63–79. editor.
  • Van Dongen HP, Baynard MD, Maislin G, Dinges DF. Systematic interindividual differences in neurobehavioral impairment from sleep loss: evidence of trait-like differential vulnerability. Sleep. 2004;27:423–433. [PubMed]
  • Tucker AM, Dinges DF, Van Dongen HP. Trait interindividual differences in the sleep physiology of healthy young adults. J Sleep Res. 2007;16:170–180. [PubMed]
  • Van Dongen HP, Maislin G, Mullington JM, Dinges DF. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep. 2003;26:117–126. [PubMed]
  • Belenky G, Wesensten NJ, Thorne DR, Thomas ML, Sing HC, et al. Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study. J Sleep Res. 2003;12:1–12. [PubMed]
  • Ganguly-Fitzgerald I, Donlea J, Shaw PJ. Waking experience affects sleep need in Drosophila. Science. 2006;313:1775–1781. [PubMed]
  • Rattenborg NC, Mandt BH, Obermeyer WH, Winsauer PJ, Huber R, et al. Migratory sleeplessness in the white-crowned sparrow (Zonotrichia leucophrys gambelii) PLoS Biol. 2004;2:e212. doi: 10.1371/journal.pbio.0020212. [PMC free article] [PubMed]
  • Tartar JL, Ward CP, McKenna JT, Thakkar M, Arrigoni E, et al. Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation. Eur J Neurosci. 2006;23:2739–2748. [PMC free article] [PubMed]
  • Jones BE. From waking to sleeping: neuronal and chemical substrates. Trends Pharmacol Sci. 2005;26:578–586. [PubMed]
  • Wesensten NJ, Killgore WD, Balkin TJ. Performance and alertness effects of caffeine, dextroamphetamine, and modafinil during sleep deprivation. J Sleep Res. 2005;14:255–266. [PubMed]
  • Braun AR, Balkin TJ, Wesenten NJ, Carson RE, Varga M, et al. Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET study. Brain. 1997;120:1173–1197. [PubMed]
  • Maquet P, Degueldre C, Delfiore G, Aerts J, Péters JM, et al. Functional neuroanatomy of human slow wave sleep. J Neurosci. 1997;17:2807–2812. [PubMed]
  • Andersson JL, Onoe H, Hetta J, Lidstrom K, Valind S, et al. Brain networks affected by synchronized sleep visualized by positron emission tomography. J Cereb Blood Flow Metab. 1998;18:701–715. [PubMed]
  • Nofzinger EA, Buysse DJ, Miewald JM, Meltzer CC, Price JC, et al. Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking. Brain. 2002;125:1105–1115. [PubMed]
  • Steriade M, Timofeev I, Grenier F. Natural waking and sleep states, a view from inside neocortical neurons. J Neurophysiol. 2001;85:1969–1985. [PubMed]
  • Maquet P. Functional neuroimaging of normal human sleep by positron emission tomography. J Sleep Res. 2000;9:207–231. [PubMed]
  • Parmeggiani PL. Thermoregulation and sleep. Front Biosci. 2003;8:s557–567. [PubMed]
  • Knutson KL, Spiegel K, Penev P, Van Cauter E. The metabolic consequences of sleep deprivation. Sleep Med Rev. 2007;11:163–178. [PMC free article] [PubMed]
  • Mednick SC, Nakayama K, Cantero JL, Atienza M, Levin AA, et al. The restorative effect of naps on perceptual deterioration. Nat Neurosci. 2002;5:677–681. [PubMed]
  • Benington JH, Heller HC. Restoration of brain energy metabolism as the function of sleep. Prog Neurobiol. 1995;45:347–360. [PubMed]
  • Franken P, Gip P, Hagiwara G, Ruby NF, Heller HC. Changes in brain glycogen after sleep deprivation vary with genotype. Am J Physiol Regul Integr Comp Physiol. 2003;285:R413–419. [PubMed]
  • Franken P, Gip P, Hagiwara G, Ruby NF, Heller HC. Glycogen content in the cerebral cortex increases with sleep loss in C57BL/6J mice. Neurosci Lett. 2006;402:176–179. [PubMed]
  • Reimund E. The free radical flux theory of sleep. Med Hypotheses. 1994;43:231–233. [PubMed]
  • Inoue S, Honda K, Komoda Y. Sleep as neuronal detoxification and restitution. Behav Brain Res. 1995;69:91–96. [PubMed]
  • Gopalakrishnan A, Ji LL, Cirelli C. Sleep deprivation and cellular responses to oxidative stress. Sleep. 2004;27:27–35. [PubMed]
  • Everson CA, Laatsch CD, Hogg N. Antioxidant defense responses to sleep loss and sleep recovery. Am J Physiol Regul Integr Comp Physiol. 2005;288:R374–383. [PubMed]
  • Cirelli C, Gutierrez CM, Tononi G. Extensive and divergent effects of sleep and wakefulness on brain gene expression. Neuron. 2004;41:35–43. [PubMed]
  • Naidoo N, Giang W, Galante RJ, Pack AI. Sleep deprivation induces the unfolded protein response in mouse cerebral cortex. J Neurochem. 2005;92:1150–1157. [PubMed]
  • Cirelli C, Tononi G. Gene expression in the brain across the sleep-waking cycle. Brain Res. 2000;885:303–321. [PubMed]
  • Cirelli C, Faraguna U, Tononi G. Changes in brain gene expression after long-term sleep deprivation. J Neurochem. 2006;98:1632–1645. [PubMed]
  • Terao A, Greco MA, Davis RW, Heller HC, Kilduff TS. Region-specific changes in immediate early gene expression in response to sleep deprivation and recovery sleep in the mouse brain. Neuroscience. 2003;120:1115–1124. [PubMed]
  • Terao A, Steininger TL, Hyder K, Apte-Deshpande A, Ding J, et al. Differential increase in the expression of heat shock protein family members during sleep deprivation and during sleep. Neuroscience. 2003;116:187–200. [PubMed]
  • Terao A, Wisor JP, Peyron C, Apte-Deshpande A, Wurts SW, et al. Gene expression in the rat brain during sleep deprivation and recovery sleep: an Affymetrix GeneChip study. Neuroscience. 2006;137:593–605. [PubMed]
  • Mackiewicz M, Shockley KR, Romer MA, Galante RJ, Zimmerman JE, et al. Macromolecule biosynthesis—a key function of sleep. Physiol Genomics. 2007;31:441–457. [PubMed]
  • Maret S, Dorsaz S, Gurcel L, Pradervand S, Petit B, et al. Homer1a is a core brain molecular correlate of sleep loss. Proc Natl Acad Sci U S A. 2007;104:20090–20095. [PMC free article] [PubMed]
  • Jones S, Pfister-Genskow M, Benca RM, Cirelli C. Molecular correlates of sleep and wakefulness in the brain of the white-crowned sparrow. J Neurochem. 2008;105:46–62. [PubMed]
  • Tononi G, Cirelli C. Sleep and synaptic homeostasis: a hypothesis. Brain Res Bull. 2003;62:143–150. [PubMed]
  • Tononi G, Cirelli C. Sleep function and synaptic homeostasis. Sleep Med Rev. 2006;10:49–62. [PubMed]
  • Attwell D, Laughlin SB. An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab. 2001;21:1133–1145. [PubMed]
  • Rothman DL, Behar KL, Hyder F, Shulman RG. In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function. Annu Rev Physiol. 2003;65:401–427. [PubMed]
  • Chklovskii DB, Schikorski T, Stevens CF. Wiring optimization in cortical circuits. Neuron. 2002;34:341–347. [PubMed]
  • Steriade M, Hobson J. Neuronal activity during the sleep-waking cycle. Prog Neurobiol. 1976;6:155–376. [PubMed]
  • Kavanau JL. Memory, sleep and the evolution of mechanisms of synaptic efficacy maintenance. Neuroscience. 1997;79:7–44. [PubMed]
  • Krueger JM, Obal F. A neuronal group theory of sleep function. J Sleep Res. 1993;2:63–69. [PubMed]
  • Krueger JM, Obal F., Jr Sleep function. Front Biosci. 2003;8:d511–519. [PubMed]
  • Giuditta A, Ambrosini MV, Montagnese P, Mandile P, Cotugno M, et al. The sequential hypothesis of the function of sleep. Behav Brain Res. 1995;69:157–166. [PubMed]
  • Marks GA, Shaffery JP, Oksenberg A, Speciale SG, Roffwarg HP. A functional role for REM sleep in brain maturation. Behav Brain Res. 1995;69:1–11. [PubMed]
  • Jouvet M. Paradoxical sleep as a programming system. J Sleep Res. 1998;7(Suppl 1):1–5. [PubMed]
  • Tononi G, Cirelli C. Some considerations on sleep and neural plasticity. Arch Ital Biol. 2001;139:221–241. [PubMed]
  • Born J, Rasch B, Gais S. Sleep to remember. Neuroscientist. 2006;12:410–424. [PubMed]
  • Stickgold R, Walker MP. Sleep-dependent memory consolidation and reconsolidation. Sleep Med. 2007;8:331–343. [PMC free article] [PubMed]
  • Steriade M. Coherent oscillations and short-term plasticity in corticothalamic networks. Trends Neurosci. 1999;22:337–345. [PubMed]
  • Sejnowski TJ, Destexhe A. Why do we sleep. Brain Res. 2000;886:208–223. [PubMed]
  • Wilson MA, McNaughton BL. Reactivation of hippocampal ensemble memories during sleep. Science. 1994;265:676–679. [PubMed]
  • Peigneux P, Laureys S, Fuchs S, Collette F, Perrin F, et al. Are spatial memories strengthened in the human hippocampus during slow wave sleep. Neuron. 2004;44:535–545. [PubMed]
  • Nadasdy Z, Hirase H, Czurko A, Csicsvari J, Buzsaki G. Replay and time compression of recurring spike sequences in the hippocampus. J Neurosci. 1999;19:9497–9507. [PubMed]
  • Ji D, Wilson MA. Coordinated memory replay in the visual cortex and hippocampus during sleep. Nat Neurosci. 2007;10:100–107. [PubMed]
  • Euston DR, Tatsuno M, McNaughton BL. Fast-forward playback of recent memory sequences in prefrontal cortex during sleep. Science. 2007;318:1147–1150. [PubMed]
  • Hill S, Tononi G, Ghilardi MF. Sleep improves the variability of motor performance. Brain Res Bull. 2008;76:605–611. [PMC free article] [PubMed]
  • Tobler II, Neuner-Jehle M. 24-h variation of vigilance in the cockroach Blaberus giganteus. J Sleep Res. 1992;1:231–239. [PubMed]
  • Tobler I. Effect of forced locomotion on the rest-activity cycle of the cockroach. Behav Brain Res. 1983;8:351–360. [PubMed]
  • Kaiser W, Steiner-Kaiser J. Neuronal correlates of sleep, wakefulness and arousal in a diurnal insect. Nature. 1983;301:707–709. [PubMed]
  • Kaiser W. Busy bees need rest, too. Behavioral and electromyographic sleep signs in honeybees. J Comp Physiol A. 1988;163:565–584.
  • Sauer S, Kinkelin M, Herrmann E, Kaiser W. The dynamics of sleep-like behaviour in honey bees. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2003;189:599–607. [PubMed]
  • Sauer S, Herrmann E, Kaiser W. Sleep deprivation in honey bees. J Sleep Res. 2004;13:145–152. [PubMed]
  • Tobler I, Borbely AA. Effect of rest deprivation on motor activity of fish. J Comp Physiol [A] 1985;157:817–822. [PubMed]
  • Shapiro CM, Hepburn HR. Sleep in a schooling fish, Tilapia mossambica. Physiol Behav. 1976;16:613–615. [PubMed]
  • Jones S, Vyazovskiy VV, Cirelli C, Tononi G, Benca RM. Homeostatic regulation of sleep in the white-crowned sparrow (Zonotrichia leucophrys gambelii) BMC Neurosci. 2008;9:47. [PMC free article] [PubMed]
  • Flanigan WF. Nocturnal behavior of small cetaceans. I. The bottlenosed porpoise, Tursiops truncatus. Sleep Res. 1974;3:84.
  • Rattenborg NC, Amlaner CJ, Lima SL. Behavioral, neurophysiological and evolutionary perspectives on unihemispheric sleep. Neurosci Biobehav Rev. 2000;24:817–842. [PubMed]
  • Ridgway S, Houser D, Finneran J, Carder D, Keogh M, et al. Functional imaging of dolphin brain metabolism and blood flow. J Exp Biol. 2006;209:2902–2910. [PubMed]
  • Ridgway S, Carder D, Finneran J, Keogh M, Kamolnick T, et al. Dolphin continuous auditory vigilance for five days. J Exp Biol. 2006;209:3621–3628. [PubMed]
  • Lyamin O, Pryaslova J, Lance V, Siegel J. Animal behaviour: continuous activity in cetaceans after birth. Nature. 2005;435:1177. [PubMed]
  • Gnone G, Moriconi T, Gambini G. Sleep behaviour: activity and sleep in dolphins. Nature. 2006;441:E10–11. [PubMed]
  • Sekiguchi Y, Arai K, Kohshima S. Sleep behaviour: sleep in continuously active dolphins. Nature. 2006;441:E9–10. [PubMed]

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