Citation: Cirelli C, Tononi G (2008) Is Sleep Essential? PLoS Biol 6(8): e216. https://doi.org/10.1371/journal.pbio.0060216
Published: August 26, 2008
Copyright: © 2008 Cirelli and Tononi. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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).
Abbreviations: EEG, electroencephalogram; NREM, non-rapid eye movement; SWA, slow-wave activity
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 , 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 . 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 .
It has been argued that the assumption that sleep is universal is based on poor evidence . 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 . 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 . 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.
See references [113–121]. SD, sleep deprivation.
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 ), and another  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 ). 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 , 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 . 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.
Dolphins and a few other species have developed unihemispheric (one-sided) sleep, a remarkable specialization strongly suggesting that sleep must have some essential function and cannot be eliminated . Yet, the very presence of sleep in dolphins has recently been questioned based on four lines of evidence. (1) It has been argued that unihemispheric sleep is not really sleep because dolphins move and, more crucially, because there is no evidence that the hemisphere with slow waves is less capable of responding to the environment . In fact, the presence of slow waves in one hemisphere is associated with unilateral slow waves in the thalamus, and unilateral decrease in brain metabolism, including in the ipsilateral locus coeruleus, an arousal-promoting system . In other words, electrophysiological and metabolic processes that always occur bilaterally in the brain of other mammals can be engaged unilaterally in the brain of a dolphin. It therefore seems at least plausible that half of the dolphin brain can be unresponsive while the other half may be awake. Indeed, there are a few brief reports showing that both bottle-nosed and white-sided dolphins show reduced or no response to stimuli when performing stereotypical circular swimming, which is associated with unihemispheric sleep [122,125].
(2) Another argument was raised by a report describing continuous activity in newborn dolphins (and whales) and their mothers for the first postpartum month . However, based on 2 additional recent studies that assessed eye closure under water [127,128], it seems likely that young cetaceans engage in unihemispheric sleep while swimming, and do so from birth for many hours a day. It has been argued  that even if present, this unihemispheric sleep could not be restorative, because it is interrupted every 30–60 s by breathing. The basis for the latter assumption remains unclear. Rats sleep 12–14 h per day and their sleep cycle lasts approximately 10–20 min. When forced to a schedule of 30-s stimulation on/90-s stimulation off, rats learn quickly to sleep in the 90-s off period, so that their total daily time in NREM sleep does not change (and the intensity increases ). When tested in a spatial learning task, these animals, which are not capable of unihemispheric sleep, still perform at 70%–80% of baseline levels. Until (if ever) combined EEG-performance studies will be performed in young cetaceans, it seems at the very least premature to imply that their sleep must necessarily be poor and not restorative. Even so, the issue is not how well they sleep, but whether they sleep.
(3) Regarding sleep homeostasis, there is only one publication  in which EEG recordings were used in dolphins to measure the response to sleep deprivation. Of note, the study used different lengths of sleep deprivation (35–150 h) and of recovery (9–24 h), slow waves could not be totally prevented during the sleep deprivation, recovery ended at different time of day, data were averaged for the entire recovery period, and only sleep duration (not sleep intensity) was measured. Nevertheless, it was found that (i) during sleep deprivation the amount of stimulation required to prevent slow waves increased progressively; (ii) in all cases (n = 6) bilateral sleep deprivation increased sleep time during recovery; (iii) in all cases (n = 9) unihemispheric sleep deprivation increased sleep duration in the affected hemisphere. Though the results of this seminal study have been characterized as “very variable” , it is hard to deny the presence of a clear-cut sleep rebound.
(4) A final issue was raised by a recent study in two highly trained dolphins, which showed that they could maintain continuous vigilance for 5 d . In fact, during the stimulation period the two animals displayed resting behavior at night (floating or very slow stereotyped swimming), and response times were slower at night than during the day, suggesting that at least some rest was obtained (most likely unihemispheric sleep, as suggested by the authors). Moreover, one of the two dolphins the last night “ignored all target stimuli for 4 hours and appeared to be asleep” .
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 , 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 . 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 . 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 , 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 . Prolonged sleep deprivation is also fatal in flies , cockroaches , and humans with fatal familial insomnia, who die after developing a syndrome not unlike that seen in sleep-deprived rats . Pigeons, however, appear capable of surviving prolonged sleep deprivation . 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.
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 , zebrafish , mice , rats , rabbits , hamsters , and dolphins ). Under a chronic “total” sleep deprivation regimen, rats still sleep at least 10% of the time, due to “microsleep” episodes . 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 ) by keeping busy with pleasurable activities. (Although seriously sleep deprived humans have been reported to fall asleep even in the most dangerous situations .) 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 , 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, ), 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 . Rather, what seems to occur is a kind of “dormiveglia” (sleepwake), a mixed state that is clearly dysfunctional.
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 , birds , and rodents (e.g., ).
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 , 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 . 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 . Brain metabolism is low in NREM sleep but high in REM sleep . Thermoregulation is preserved in NREM sleep but not in REM sleep . 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 , 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 . 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 , 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 , 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 , 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 .
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 . A related idea is that an offline activation of neural circuits may be especially important during development , perhaps to rehearse innate behavioral patterns . 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 .
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.
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.
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.
- 1. Zepelin H, Rechtschaffen A (1974) Mammalian sleep, longevity, and energy metabolism. Brain Behav Evol 10: 425–470.H. ZepelinA. Rechtschaffen1974Mammalian sleep, longevity, and energy metabolism.Brain Behav Evol10425470
- 2. Campbell SS, Tobler I (1984) Animal sleep: a review of sleep duration across phylogeny. Neurosci Biobehav Rev 8: 269–300.SS CampbellI. Tobler1984Animal sleep: a review of sleep duration across phylogeny.Neurosci Biobehav Rev8269300
- 3. Lesku JA, Roth TC, Rattenborg NC, Amlaner CJ, Lima SL (2008) Phylogenetics and the correlates of mammalian sleep: A reappraisal. Sleep Med Rev 12: 229–244.JA LeskuTC RothNC RattenborgCJ AmlanerSL Lima2008Phylogenetics and the correlates of mammalian sleep: A reappraisal.Sleep Med Rev12229244
- 4. Capellini I, Barton RA, McNamara P, Preston BT, Nunn CL (2008) Phylogenetic analysis of the ecology and evolution of mammalian sleep. Evolution. I. CapelliniRA BartonP. McNamaraBT PrestonCL Nunn2008Phylogenetic analysis of the ecology and evolution of mammalian sleep.EvolutionE-pub ahead of print. doi:10.1111/j.1558-5646.2008.00392.x. E-pub ahead of print. doi:10.1111/j.1558-5646.2008.00392.x.
- 5. Meddis R (1975) On the function of sleep. Anim Behav 23: 676–691.R. Meddis1975On the function of sleep.Anim Behav23676691
- 6. Rial RV, Nicolau MC, Gamundi A, Akaarir M, Aparicio S, et al. (2007) The trivial function of sleep. Sleep Med Rev 11: 311–325.RV RialMC NicolauA. GamundiM. AkaarirS. Aparicio2007The trivial function of sleep.Sleep Med Rev11311325
- 7. Siegel JM (2008) Do all animals sleep. Trends Neurosci 31: 208–213.JM Siegel2008Do all animals sleep.Trends Neurosci31208213
- 8. Horne JA (1985) Sleep function, with particular reference to sleep deprivation. Ann CLin Res 17: 199–208.JA Horne1985Sleep function, with particular reference to sleep deprivation.Ann CLin Res17199208
- 9. Rechtschaffen A (1998) Current perspectives on the function of sleep. Perspect Biol Med 41: 359–390.A. Rechtschaffen1998Current perspectives on the function of sleep.Perspect Biol Med41359390
- 10. Mignot E (2008) Why we sleep: the temporal organization of recovery. PLoS Biol 6: e106.E. Mignot2008Why we sleep: the temporal organization of recovery.PLoS Biol6e106
- 11. Hendricks JC, Finn SM, Panckeri KA, Chavkin J, Williams JA, et al. (2000) Rest in Drosophila is a sleep-like state. Neuron 25: 129–138.JC HendricksSM FinnKA PanckeriJ. ChavkinJA Williams2000Rest in Drosophila is a sleep-like state.Neuron25129138
- 12. Shaw PJ, Cirelli C, Greenspan RJ, Tononi G (2000) Correlates of sleep and waking in Drosophila melanogaster. Science 287: 1834–1837.PJ ShawC. CirelliRJ GreenspanG. Tononi2000Correlates of sleep and waking in Drosophila melanogaster.Science28718341837
- 13. Cirelli C (2003) Searching for sleep mutants of Drosophila melanogaster. Bioessays 25: 940–949.C. Cirelli2003Searching for sleep mutants of Drosophila melanogaster.Bioessays25940949
- 14. Shaw P (2003) Awakening to the behavioral analysis of sleep in Drosophila. J Biol Rhythms 18: 4–11.P. Shaw2003Awakening to the behavioral analysis of sleep in Drosophila.J Biol Rhythms18411
- 15. Ho KS, Sehgal A (2005) Drosophila melanogaster: An insect model for fundamental studies of sleep. Methods Enzymol 393: 772–793.KS HoA. Sehgal2005Drosophila melanogaster: An insect model for fundamental studies of sleep.Methods Enzymol393772793
- 16. Cirelli C, LaVaute TM, Tononi G (2005) Sleep and wakefulness modulate gene expression in Drosophila. J Neurochem 94: 1411–1419.C. CirelliTM LaVauteG. Tononi2005Sleep and wakefulness modulate gene expression in Drosophila.J Neurochem9414111419
- 17. Zimmerman JE, Rizzo W, Shockley KR, Raizen DM, Naidoo N, et al. (2006) Multiple mechanisms limit the duration of wakefulness in Drosophila brain. Physiol Genomics 27: 337–350.JE ZimmermanW. RizzoKR ShockleyDM RaizenN. Naidoo2006Multiple mechanisms limit the duration of wakefulness in Drosophila brain.Physiol Genomics27337350
- 18. Nitz DA, van Swinderen B, Tononi G, Greenspan RJ (2002) Electrophysiological correlates of rest and activity in Drosophila melanogaster. Curr Biol 12: 1934–1940.DA NitzB. van SwinderenG. TononiRJ Greenspan2002Electrophysiological correlates of rest and activity in Drosophila melanogaster.Curr Biol1219341940
- 19. Zhdanova IV, Wang SY, Leclair OU, Danilova NP (2001) Melatonin promotes sleep-like state in zebrafish. Brain Res 903: 263–268.IV ZhdanovaSY WangOU LeclairNP Danilova2001Melatonin promotes sleep-like state in zebrafish.Brain Res903263268
- 20. Prober DA, Rihel J, Onah AA, Sung RJ, Schier AF (2006) Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish. J Neurosci 26: 13400–13410.DA ProberJ. RihelAA OnahRJ SungAF Schier2006Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish.J Neurosci261340013410
- 21. Yokogawa T, Marin W, Faraco J, Pezeron G, Appelbaum L, et al. (2007) Characterization of sleep in zebrafish and insomnia in hypocretin receptor mutants. PLoS Biol 5: e277.T. YokogawaW. MarinJ. FaracoG. PezeronL. Appelbaum2007Characterization of sleep in zebrafish and insomnia in hypocretin receptor mutants.PLoS Biol5e277
- 22. Raizen DM, Zimmerman JE, Maycock MH, Ta UD, You YJ, et al. (2008) Lethargus is a Caenorhabditis elegans sleep-like state. Nature 451: 569–572.DM RaizenJE ZimmermanMH MaycockUD TaYJ You2008Lethargus is a Caenorhabditis elegans sleep-like state.Nature451569572
- 23. Hobson JA (1967) Electrographic correlates of behavior in the frog with special reference to sleep. Electroencephalogr Clin Neurophysiol 22: 113–121.JA Hobson1967Electrographic correlates of behavior in the frog with special reference to sleep.Electroencephalogr Clin Neurophysiol22113121
- 24. Tauber ES, Weitzman ED (1969) Eye movements during behavioral inactivity in certain Bermuda reef fish. Commun Behav Biol 3: 131–135.ES TauberED Weitzman1969Eye movements during behavioral inactivity in certain Bermuda reef fish.Commun Behav Biol3131135
- 25. Goldshmid R, Holzman R, Weihs D, Genin A (2004) Aeration of corals by sleep-swimming fish. Limnol Oceanogr 49: 1832–1839.R. GoldshmidR. HolzmanD. WeihsA. Genin2004Aeration of corals by sleep-swimming fish.Limnol Oceanogr4918321839
- 26. Holbrook SJ, Schmitt RJ (2002) Competition for shelter space causes density-dependent predation mortality in damselfishes. Ecology 83: 2855–2868.SJ HolbrookRJ Schmitt2002Competition for shelter space causes density-dependent predation mortality in damselfishes.Ecology8328552868
- 27. Mukhametov LM, Supin AY, Polyakova IG (1977) Interhemispheric asymmetry of the electroencephalographic sleep patterns in dolphins. Brain Res 134: 581–584.LM MukhametovAY SupinIG Polyakova1977Interhemispheric asymmetry of the electroencephalographic sleep patterns in dolphins.Brain Res134581584
- 28. Mukhametov LM (1987) Unihemispheric slow-wave sleep in the Amazonian dolphin, Inia geoffrensis. Neurosci Lett 79: 128–132.LM Mukhametov1987Unihemispheric slow-wave sleep in the Amazonian dolphin, Inia geoffrensis.Neurosci Lett79128132
- 29. Ridgway SH (2002) 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 60: 265–274.SH Ridgway2002Asymmetry 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 Evol60265274
- 30. Lyamin OI, Mukhametov LM, Chetyrbok IS, Vassiliev AV (2002) Sleep and wakefulness in the southern sea lion. Behav Brain Res 128: 129–138.OI LyaminLM MukhametovIS ChetyrbokAV Vassiliev2002Sleep and wakefulness in the southern sea lion.Behav Brain Res128129138
- 31. Lyamin OI, Mukhametov LM, Siegel JM, Nazarenko EA, Polyakova IG, et al. (2002) Unihemispheric slow wave sleep and the state of the eyes in a white whale. Behav Brain Res 129: 125–129.OI LyaminLM MukhametovJM SiegelEA NazarenkoIG Polyakova2002Unihemispheric slow wave sleep and the state of the eyes in a white whale.Behav Brain Res129125129
- 32. Tobler I (1995) Is sleep fundamentally different between mammalian species. Behav Brain Res 69: 35–41.I. Tobler1995Is sleep fundamentally different between mammalian species.Behav Brain Res693541
- 33. (2005) Phylogeny of sleep regulation. In: Kryger MH, Roth T, Dement WC, editors. Principles and practice of sleep medicine. 4th edition. Philadelphia: Elsevier Saunders. pp. 77–90.I. Tobler2005Phylogeny of sleep regulation.In. MH KrygerT. RothWC Dementeditors. Principles and practice of sleep medicine4th editionPhiladelphiaElsevier Saunders7790 editors.
- 34. Berger RJ, Phillips NH (1994) Constant light suppresses sleep and circadian rhythms in pigeons without consequent sleep rebound in darkness. Am J Physiol 267: R945–952.RJ BergerNH Phillips1994Constant light suppresses sleep and circadian rhythms in pigeons without consequent sleep rebound in darkness.Am J Physiol267R945952
- 35. Achermann P, Borbely AA (2003) Mathematical models of sleep regulation. Front Biosci 8: S683–693.P. AchermannAA Borbely2003Mathematical models of sleep regulation.Front Biosci8S683693
- 36. Rechtschaffen A, Bergmann BM (2002) Sleep deprivation in the rat: an update of the 1989 paper. Sleep 25: 18–24.A. RechtschaffenBM Bergmann2002Sleep deprivation in the rat: an update of the 1989 paper.Sleep251824
- 37. Shaw PJ, Tononi G, Greenspan RJ, Robinson DF (2002) Stress response genes protect against lethal effects of sleep deprivation in Drosophila. Nature 417: 287–291.PJ ShawG. TononiRJ GreenspanDF Robinson2002Stress response genes protect against lethal effects of sleep deprivation in Drosophila.Nature417287291
- 38. Stephenson R, Chu KM, Lee J (2007) Prolonged deprivation of sleep-like rest raises metabolic rate in the Pacific beetle cockroach, Diploptera punctata (Eschscholtz). J Exp Biol 210: 2540–2547.R. StephensonKM ChuJ. Lee2007Prolonged deprivation of sleep-like rest raises metabolic rate in the Pacific beetle cockroach, Diploptera punctata (Eschscholtz).J Exp Biol21025402547
- 39. Montagna P, Lugaresi E (2002) Agrypnia excitata: a generalized overactivity syndrome and a useful concept in the neurophysiopathology of sleep. Clin Neurophysiol 113: 552–560.P. MontagnaE. Lugaresi2002Agrypnia excitata: a generalized overactivity syndrome and a useful concept in the neurophysiopathology of sleep.Clin Neurophysiol113552560
- 40. Newman SM, Paletz EM, Rattenborg NC, Obermeyer WH, Benca RM (2008) Sleep deprivation in the pigeon using the disk-over-water method. Physiol Behav 93: 50–58.SM NewmanEM PaletzNC RattenborgWH ObermeyerRM Benca2008Sleep deprivation in the pigeon using the disk-over-water method.Physiol Behav935058
- 41. Franken P, Malafosse A, Tafti M (1999) Genetic determinants of sleep regulation in inbred mice. Sleep 22: 155–169.P. FrankenA. MalafosseM. Tafti1999Genetic determinants of sleep regulation in inbred mice.Sleep22155169
- 42. Franken P, Dijk D, Tobler I, Borbely A (1991) Sleep deprivation in the rat: effects of electroencephalogram power spectra, vigilance states, and cortical temperature. Am J Physiol 261: R198–208.P. FrankenD. DijkI. ToblerA. Borbely1991Sleep deprivation in the rat: effects of electroencephalogram power spectra, vigilance states, and cortical temperature.Am J Physiol261R198208
- 43. Tobler I, Franken P, Scherschlicht R (1990) Sleep and EEG spectra in the rabbit under baseline conditions and following sleep deprivation. Physiol Behav 48: 121–129.I. ToblerP. FrankenR. Scherschlicht1990Sleep and EEG spectra in the rabbit under baseline conditions and following sleep deprivation.Physiol Behav48121129
- 44. Larkin JE, Yokogawa T, Heller HC, Franken P, Ruby NF (2004) Homeostatic regulation of sleep in arrhythmic Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 287: R104–111.JE LarkinT. YokogawaHC HellerP. FrankenNF Ruby2004Homeostatic regulation of sleep in arrhythmic Siberian hamsters.Am J Physiol Regul Integr Comp Physiol287R104111
- 45. Oleksenko AI, Mukhametov LM, Polyakova IG, Supin AY, Kovalzon VM (1992) Unihemispheric sleep deprivation in bottlenose dolphins. J Sleep Res 1: 40–44.AI OleksenkoLM MukhametovIG PolyakovaAY SupinVM Kovalzon1992Unihemispheric sleep deprivation in bottlenose dolphins.J Sleep Res14044
- 46. Friedman L, Bergmann BM, Rechtschaffen A (1979) Effects of sleep deprivation on sleepiness, sleep intensity, and subsequent sleep in the rat. Sleep 1: 369–391.L. FriedmanBM BergmannA. Rechtschaffen1979Effects of sleep deprivation on sleepiness, sleep intensity, and subsequent sleep in the rat.Sleep1369391
- 47. Gulevich G, Dement W, Johnson L (1966) Psychiatric and EEG observations on a case of prolonged (264 hours) wakefulness. Arch Gen Psychiatry 15: 29–35.G. GulevichW. DementL. Johnson1966Psychiatric and EEG observations on a case of prolonged (264 hours) wakefulness.Arch Gen Psychiatry152935
- 48. Rogers NL, Dorrian J, Dinges DF (2003) Sleep, waking and neurobehavioural performance. Front Biosci 8: s1056–1067.NL RogersJ. DorrianDF Dinges2003Sleep, waking and neurobehavioural performance.Front Biosci8s10561067
- 49. Naitoh P, Kales A, Kollar EJ, Smith JC, Jacobson A (1969) Electroencephalographic activity after prolonged sleep loss. Electroencephalogr Clin Neurophysiol 27: 2–11.P. NaitohA. KalesEJ KollarJC SmithA. Jacobson1969Electroencephalographic activity after prolonged sleep loss.Electroencephalogr Clin Neurophysiol27211
- 50. Cajochen C, Khalsa SB, 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 277: R640–649.C. CajochenSB KhalsaJK WyattCA CzeislerDJ Dijk1999EEG and ocular correlates of circadian melatonin phase and human performance decrements during sleep loss.Am J Physiol277R640649
- 51. 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.C. CajochenJK WyattCA CzeislerDJ Dijk2002Separation of circadian and wake duration-dependent modulation of EEG activation during wakefulness.Neuroscience11410471060
- 52. Pigarev IN, Nothdurft HC, Kastner S (1997) Evidence for asynchronous development of sleep in cortical areas. Neuroreport 8: 2557–2560.IN PigarevHC NothdurftS. Kastner1997Evidence for asynchronous development of sleep in cortical areas.Neuroreport825572560
- 53. Rector DM, Topchiy IA, Carter KM, Rojas MJ (2005) Local functional state differences between rat cortical columns. Brain Res 1047: 45–55.DM RectorIA TopchiyKM CarterMJ Rojas2005Local functional state differences between rat cortical columns.Brain Res10474555
- 54. (2005) Total sleep deprivation. In: Kushida CA, editor. Sleep deprivation: basic science, physiology, and behavior. New York, NY: Marcel Dekker. pp. 63–79.C. CirelliG. Tononi2005Total sleep deprivation.In. CA Kushidaeditor. Sleep deprivation: basic science, physiology, and behaviorNew York, NYMarcel Dekker6379 editor.
- 55. Van Dongen HP, Baynard MD, Maislin G, Dinges DF (2004) Systematic interindividual differences in neurobehavioral impairment from sleep loss: evidence of trait-like differential vulnerability. Sleep 27: 423–433.HP Van DongenMD BaynardG. MaislinDF Dinges2004Systematic interindividual differences in neurobehavioral impairment from sleep loss: evidence of trait-like differential vulnerability.Sleep27423433
- 56. Tucker AM, Dinges DF, Van Dongen HP (2007) Trait interindividual differences in the sleep physiology of healthy young adults. J Sleep Res 16: 170–180.AM TuckerDF DingesHP Van Dongen2007Trait interindividual differences in the sleep physiology of healthy young adults.J Sleep Res16170180
- 57. Van Dongen HP, 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.HP Van DongenG. MaislinJM MullingtonDF Dinges2003The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation.Sleep26117126
- 58. Belenky G, Wesensten NJ, Thorne DR, Thomas ML, Sing HC, et al. (2003) Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study. J Sleep Res 12: 1–12.G. BelenkyNJ WesenstenDR ThorneML ThomasHC Sing2003Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study.J Sleep Res12112
- 59. Ganguly-Fitzgerald I, Donlea J, Shaw PJ (2006) Waking experience affects sleep need in Drosophila. Science 313: 1775–1781.I. Ganguly-FitzgeraldJ. DonleaPJ Shaw2006Waking experience affects sleep need in Drosophila.Science31317751781
- 60. Rattenborg NC, Mandt BH, Obermeyer WH, Winsauer PJ, Huber R, et al. (2004) Migratory sleeplessness in the white-crowned sparrow (Zonotrichia leucophrys gambelii). PLoS Biol 2: e212.NC RattenborgBH MandtWH ObermeyerPJ WinsauerR. Huber2004Migratory sleeplessness in the white-crowned sparrow (Zonotrichia leucophrys gambelii).PLoS Biol2e212
- 61. Tartar JL, Ward CP, McKenna JT, Thakkar M, Arrigoni E, et al. (2006) Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation. Eur J Neurosci 23: 2739–2748.JL TartarCP WardJT McKennaM. ThakkarE. Arrigoni2006Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation.Eur J Neurosci2327392748
- 62. Jones BE (2005) From waking to sleeping: neuronal and chemical substrates. Trends Pharmacol Sci 26: 578–586.BE Jones2005From waking to sleeping: neuronal and chemical substrates.Trends Pharmacol Sci26578586
- 63. Wesensten NJ, Killgore WD, Balkin TJ (2005) Performance and alertness effects of caffeine, dextroamphetamine, and modafinil during sleep deprivation. J Sleep Res 14: 255–266.NJ WesenstenWD KillgoreTJ Balkin2005Performance and alertness effects of caffeine, dextroamphetamine, and modafinil during sleep deprivation.J Sleep Res14255266
- 64. Braun AR, Balkin TJ, Wesenten NJ, Carson RE, Varga M, et al. (1997) Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET study. Brain 120: 1173–1197.AR BraunTJ BalkinNJ WesentenRE CarsonM. Varga1997Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET study.Brain12011731197
- 65. Maquet P, Degueldre C, Delfiore G, Aerts J, Péters JM, et al. (1997) Functional neuroanatomy of human slow wave sleep. J Neurosci 17: 2807–2812.P. MaquetC. DegueldreG. DelfioreJ. AertsJM Péters1997Functional neuroanatomy of human slow wave sleep.J Neurosci1728072812
- 66. Andersson JL, Onoe H, Hetta J, Lidstrom K, Valind S, et al. (1998) Brain networks affected by synchronized sleep visualized by positron emission tomography. J Cereb Blood Flow Metab 18: 701–715.JL AnderssonH. OnoeJ. HettaK. LidstromS. Valind1998Brain networks affected by synchronized sleep visualized by positron emission tomography.J Cereb Blood Flow Metab18701715
- 67. Nofzinger EA, Buysse DJ, Miewald JM, Meltzer CC, Price JC, et al. (2002) Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking. Brain 125: 1105–1115.EA NofzingerDJ BuysseJM MiewaldCC MeltzerJC Price2002Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking.Brain12511051115
- 68. Steriade M, Timofeev I, Grenier F (2001) Natural waking and sleep states, a view from inside neocortical neurons. J Neurophysiol 85: 1969–1985.M. SteriadeI. TimofeevF. Grenier2001Natural waking and sleep states, a view from inside neocortical neurons.J Neurophysiol8519691985
- 69. Maquet P (2000) Functional neuroimaging of normal human sleep by positron emission tomography. J Sleep Res 9: 207–231.P. Maquet2000Functional neuroimaging of normal human sleep by positron emission tomography.J Sleep Res9207231
- 70. Parmeggiani PL (2003) Thermoregulation and sleep. Front Biosci 8: s557–567.PL Parmeggiani2003Thermoregulation and sleep.Front Biosci8s557567
- 71. Knutson KL, Spiegel K, Penev P, Van Cauter E (2007) The metabolic consequences of sleep deprivation. Sleep Med Rev 11: 163–178.KL KnutsonK. SpiegelP. PenevE. Van Cauter2007The metabolic consequences of sleep deprivation.Sleep Med Rev11163178
- 72. Mednick SC, Nakayama K, Cantero JL, Atienza M, Levin AA, et al. (2002) The restorative effect of naps on perceptual deterioration. Nat Neurosci 5: 677–681.SC MednickK. NakayamaJL CanteroM. AtienzaAA Levin2002The restorative effect of naps on perceptual deterioration.Nat Neurosci5677681
- 73. Benington JH, Heller HC (1995) Restoration of brain energy metabolism as the function of sleep. Prog Neurobiol 45: 347–360.JH BeningtonHC Heller1995Restoration of brain energy metabolism as the function of sleep.Prog Neurobiol45347360
- 74. Franken P, Gip P, Hagiwara G, Ruby NF, Heller HC (2003) Changes in brain glycogen after sleep deprivation vary with genotype. Am J Physiol Regul Integr Comp Physiol 285: R413–419.P. FrankenP. GipG. HagiwaraNF RubyHC Heller2003Changes in brain glycogen after sleep deprivation vary with genotype.Am J Physiol Regul Integr Comp Physiol285R413419
- 75. Franken P, Gip P, Hagiwara G, Ruby NF, Heller HC (2006) Glycogen content in the cerebral cortex increases with sleep loss in C57BL/6J mice. Neurosci Lett 402: 176–179.P. FrankenP. GipG. HagiwaraNF RubyHC Heller2006Glycogen content in the cerebral cortex increases with sleep loss in C57BL/6J mice.Neurosci Lett402176179
- 76. Reimund E (1994) The free radical flux theory of sleep. Med Hypotheses 43: 231–233.E. Reimund1994The free radical flux theory of sleep.Med Hypotheses43231233
- 77. Inoue S, Honda K, Komoda Y (1995) Sleep as neuronal detoxification and restitution. Behav Brain Res 69: 91–96.S. InoueK. HondaY. Komoda1995Sleep as neuronal detoxification and restitution.Behav Brain Res699196
- 78. Gopalakrishnan A, Ji LL, Cirelli C (2004) Sleep deprivation and cellular responses to oxidative stress. Sleep 27: 27–35.A. GopalakrishnanLL JiC. Cirelli2004Sleep deprivation and cellular responses to oxidative stress.Sleep272735
- 79. Everson CA, Laatsch CD, Hogg N (2005) Antioxidant defense responses to sleep loss and sleep recovery. Am J Physiol Regul Integr Comp Physiol 288: R374–383.CA EversonCD LaatschN. Hogg2005Antioxidant defense responses to sleep loss and sleep recovery.Am J Physiol Regul Integr Comp Physiol288R374383
- 80. Cirelli C, Gutierrez CM, Tononi G (2004) Extensive and divergent effects of sleep and wakefulness on brain gene expression. Neuron 41: 35–43.C. CirelliCM GutierrezG. Tononi2004Extensive and divergent effects of sleep and wakefulness on brain gene expression.Neuron413543
- 81. Naidoo N, Giang W, Galante RJ, Pack AI (2005) Sleep deprivation induces the unfolded protein response in mouse cerebral cortex. J Neurochem 92: 1150–1157.N. NaidooW. GiangRJ GalanteAI Pack2005Sleep deprivation induces the unfolded protein response in mouse cerebral cortex.J Neurochem9211501157
- 82. Cirelli C, Tononi G (2000) Gene expression in the brain across the sleep-waking cycle. Brain Res 885: 303–321.C. CirelliG. Tononi2000Gene expression in the brain across the sleep-waking cycle.Brain Res885303321
- 83. Cirelli C, Faraguna U, Tononi G (2006) Changes in brain gene expression after long-term sleep deprivation. J Neurochem 98: 1632–1645.C. CirelliU. FaragunaG. Tononi2006Changes in brain gene expression after long-term sleep deprivation.J Neurochem9816321645
- 84. Terao A, Greco MA, Davis RW, Heller HC, Kilduff TS (2003) Region-specific changes in immediate early gene expression in response to sleep deprivation and recovery sleep in the mouse brain. Neuroscience 120: 1115–1124.A. TeraoMA GrecoRW DavisHC HellerTS Kilduff2003Region-specific changes in immediate early gene expression in response to sleep deprivation and recovery sleep in the mouse brain.Neuroscience12011151124
- 85. Terao A, Steininger TL, Hyder K, Apte-Deshpande A, Ding J, et al. (2003) Differential increase in the expression of heat shock protein family members during sleep deprivation and during sleep. Neuroscience 116: 187–200.A. TeraoTL SteiningerK. HyderA. Apte-DeshpandeJ. Ding2003Differential increase in the expression of heat shock protein family members during sleep deprivation and during sleep.Neuroscience116187200
- 86. Terao A, Wisor JP, Peyron C, Apte-Deshpande A, Wurts SW, et al. (2006) Gene expression in the rat brain during sleep deprivation and recovery sleep: an Affymetrix GeneChip study. Neuroscience 137: 593–605.A. TeraoJP WisorC. PeyronA. Apte-DeshpandeSW Wurts2006Gene expression in the rat brain during sleep deprivation and recovery sleep: an Affymetrix GeneChip study.Neuroscience137593605
- 87. Mackiewicz M, Shockley KR, Romer MA, Galante RJ, Zimmerman JE, et al. (2007) Macromolecule biosynthesis—a key function of sleep. Physiol Genomics 31: 441–457.M. MackiewiczKR ShockleyMA RomerRJ GalanteJE Zimmerman2007Macromolecule biosynthesis—a key function of sleep.Physiol Genomics31441457
- 88. Maret S, Dorsaz S, Gurcel L, Pradervand S, Petit B, et al. (2007) Homer1a is a core brain molecular correlate of sleep loss. Proc Natl Acad Sci U S A 104: 20090–20095.S. MaretS. DorsazL. GurcelS. PradervandB. Petit2007Homer1a is a core brain molecular correlate of sleep loss.Proc Natl Acad Sci U S A1042009020095
- 89. Jones S, Pfister-Genskow M, Benca RM, Cirelli C (2008) Molecular correlates of sleep and wakefulness in the brain of the white-crowned sparrow. J Neurochem 105: 46–62.S. JonesM. Pfister-GenskowRM BencaC. Cirelli2008Molecular correlates of sleep and wakefulness in the brain of the white-crowned sparrow.J Neurochem1054662
- 90. Tononi G, Cirelli C (2003) Sleep and synaptic homeostasis: a hypothesis. Brain Res Bull 62: 143–150.G. TononiC. Cirelli2003Sleep and synaptic homeostasis: a hypothesis.Brain Res Bull62143150
- 91. Tononi G, Cirelli C (2006) Sleep function and synaptic homeostasis. Sleep Med Rev 10: 49–62.G. TononiC. Cirelli2006Sleep function and synaptic homeostasis.Sleep Med Rev104962
- 92. Attwell D, Laughlin SB (2001) An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 21: 1133–1145.D. AttwellSB Laughlin2001An energy budget for signaling in the grey matter of the brain.J Cereb Blood Flow Metab2111331145
- 93. Rothman DL, Behar KL, Hyder F, Shulman RG (2003) In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function. Annu Rev Physiol 65: 401–427.DL RothmanKL BeharF. HyderRG Shulman2003In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function.Annu Rev Physiol65401427
- 94. Chklovskii DB, Schikorski T, Stevens CF (2002) Wiring optimization in cortical circuits. Neuron 34: 341–347.DB ChklovskiiT. SchikorskiCF Stevens2002Wiring optimization in cortical circuits.Neuron34341347
- 95. Steriade M, Hobson J (1976) Neuronal activity during the sleep-waking cycle. Prog Neurobiol 6: 155–376.M. SteriadeJ. Hobson1976Neuronal activity during the sleep-waking cycle.Prog Neurobiol6155376
- 96. Kavanau JL (1997) Memory, sleep and the evolution of mechanisms of synaptic efficacy maintenance. Neuroscience 79: 7–44.JL Kavanau1997Memory, sleep and the evolution of mechanisms of synaptic efficacy maintenance.Neuroscience79744
- 97. Krueger JM, Obal F (1993) A neuronal group theory of sleep function. J Sleep Res 2: 63–69.JM KruegerF. Obal1993A neuronal group theory of sleep function.J Sleep Res26369
- 98. Krueger JM, Obal F Jr (2003) Sleep function. Front Biosci 8: d511–519.JM KruegerF. Obal Jr2003Sleep function.Front Biosci8d511519
- 99. Giuditta A, Ambrosini MV, Montagnese P, Mandile P, Cotugno M, et al. (1995) The sequential hypothesis of the function of sleep. Behav Brain Res 69: 157–166.A. GiudittaMV AmbrosiniP. MontagneseP. MandileM. Cotugno1995The sequential hypothesis of the function of sleep.Behav Brain Res69157166
- 100. Marks GA, Shaffery JP, Oksenberg A, Speciale SG, Roffwarg HP (1995) A functional role for REM sleep in brain maturation. Behav Brain Res 69: 1–11.GA MarksJP ShafferyA. OksenbergSG SpecialeHP Roffwarg1995A functional role for REM sleep in brain maturation.Behav Brain Res69111
- 101. Jouvet M (1998) Paradoxical sleep as a programming system. J Sleep Res 7(Suppl 1): 1–5.M. Jouvet1998Paradoxical sleep as a programming system.J Sleep Res7Suppl 115
- 102. Tononi G, Cirelli C (2001) Some considerations on sleep and neural plasticity. Arch Ital Biol 139: 221–241.G. TononiC. Cirelli2001Some considerations on sleep and neural plasticity.Arch Ital Biol139221241
- 103. Born J, Rasch B, Gais S (2006) Sleep to remember. Neuroscientist 12: 410–424.J. BornB. RaschS. Gais2006Sleep to remember.Neuroscientist12410424
- 104. Stickgold R, Walker MP (2007) Sleep-dependent memory consolidation and reconsolidation. Sleep Med 8: 331–343.R. StickgoldMP Walker2007Sleep-dependent memory consolidation and reconsolidation.Sleep Med8331343
- 105. Steriade M (1999) Coherent oscillations and short-term plasticity in corticothalamic networks. Trends Neurosci 22: 337–345.M. Steriade1999Coherent oscillations and short-term plasticity in corticothalamic networks.Trends Neurosci22337345
- 106. Sejnowski TJ, Destexhe A (2000) Why do we sleep. Brain Res 886: 208–223.TJ SejnowskiA. Destexhe2000Why do we sleep.Brain Res886208223
- 107. Wilson MA, McNaughton BL (1994) Reactivation of hippocampal ensemble memories during sleep. Science 265: 676–679.MA WilsonBL McNaughton1994Reactivation of hippocampal ensemble memories during sleep.Science265676679
- 108. Peigneux P, Laureys S, Fuchs S, Collette F, Perrin F, et al. (2004) Are spatial memories strengthened in the human hippocampus during slow wave sleep. Neuron 44: 535–545.P. PeigneuxS. LaureysS. FuchsF. ColletteF. Perrin2004Are spatial memories strengthened in the human hippocampus during slow wave sleep.Neuron44535545
- 109. Nadasdy Z, Hirase H, Czurko A, Csicsvari J, Buzsaki G (1999) Replay and time compression of recurring spike sequences in the hippocampus. J Neurosci 19: 9497–9507.Z. NadasdyH. HiraseA. CzurkoJ. CsicsvariG. Buzsaki1999Replay and time compression of recurring spike sequences in the hippocampus.J Neurosci1994979507
- 110. Ji D, Wilson MA (2007) Coordinated memory replay in the visual cortex and hippocampus during sleep. Nat Neurosci 10: 100–107.D. JiMA Wilson2007Coordinated memory replay in the visual cortex and hippocampus during sleep.Nat Neurosci10100107
- 111. Euston DR, Tatsuno M, McNaughton BL (2007) Fast-forward playback of recent memory sequences in prefrontal cortex during sleep. Science 318: 1147–1150.DR EustonM. TatsunoBL McNaughton2007Fast-forward playback of recent memory sequences in prefrontal cortex during sleep.Science31811471150
- 112. Hill S, Tononi G, Ghilardi MF (2008) Sleep improves the variability of motor performance. Brain Res Bull 76: 605–611.S. HillG. TononiMF Ghilardi2008Sleep improves the variability of motor performance.Brain Res Bull76605611
- 113. Tobler II, Neuner-Jehle M (1992) 24-h variation of vigilance in the cockroach Blaberus giganteus. J Sleep Res 1: 231–239.II ToblerM. Neuner-Jehle199224-h variation of vigilance in the cockroach Blaberus giganteus.J Sleep Res1231239
- 114. Tobler I (1983) Effect of forced locomotion on the rest-activity cycle of the cockroach. Behav Brain Res 8: 351–360.I. Tobler1983Effect of forced locomotion on the rest-activity cycle of the cockroach.Behav Brain Res8351360
- 115. Kaiser W, Steiner-Kaiser J (1983) Neuronal correlates of sleep, wakefulness and arousal in a diurnal insect. Nature 301: 707–709.W. KaiserJ. Steiner-Kaiser1983Neuronal correlates of sleep, wakefulness and arousal in a diurnal insect.Nature301707709
- 116. Kaiser W (1988) Busy bees need rest, too. Behavioral and electromyographic sleep signs in honeybees. J Comp Physiol A 163: 565–584.W. Kaiser1988Busy bees need rest, too. Behavioral and electromyographic sleep signs in honeybees.J Comp Physiol A163565584
- 117. Sauer S, Kinkelin M, Herrmann E, Kaiser W (2003) The dynamics of sleep-like behaviour in honey bees. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 189: 599–607.S. SauerM. KinkelinE. HerrmannW. Kaiser2003The dynamics of sleep-like behaviour in honey bees.J Comp Physiol A Neuroethol Sens Neural Behav Physiol189599607
- 118. Sauer S, Herrmann E, Kaiser W (2004) Sleep deprivation in honey bees. J Sleep Res 13: 145–152.S. SauerE. HerrmannW. Kaiser2004Sleep deprivation in honey bees.J Sleep Res13145152
- 119. Tobler I, Borbely AA (1985) Effect of rest deprivation on motor activity of fish. J Comp Physiol [A] 157: 817–822.I. ToblerAA Borbely1985Effect of rest deprivation on motor activity of fish.J Comp Physiol [A]157817822
- 120. Shapiro CM, Hepburn HR (1976) Sleep in a schooling fish, Tilapia mossambica. Physiol Behav 16: 613–615.CM ShapiroHR Hepburn1976Sleep in a schooling fish, Tilapia mossambica.Physiol Behav16613615
- 121. Jones S, Vyazovskiy VV, Cirelli C, Tononi G, Benca RM (2008) Homeostatic regulation of sleep in the white-crowned sparrow (Zonotrichia leucophrys gambelii). BMC Neurosci 9: 47.S. JonesVV VyazovskiyC. CirelliG. TononiRM Benca2008Homeostatic regulation of sleep in the white-crowned sparrow (Zonotrichia leucophrys gambelii).BMC Neurosci947
- 122. Flanigan WF (1974) Nocturnal behavior of small cetaceans. I. The bottlenosed porpoise, Tursiops truncatus. Sleep Res 3: 84.WF Flanigan1974Nocturnal behavior of small cetaceans. I. The bottlenosed porpoise, Tursiops truncatus.Sleep Res384
- 123. Rattenborg NC, Amlaner CJ, Lima SL (2000) Behavioral, neurophysiological and evolutionary perspectives on unihemispheric sleep. Neurosci Biobehav Rev 24: 817–842.NC RattenborgCJ AmlanerSL Lima2000Behavioral, neurophysiological and evolutionary perspectives on unihemispheric sleep.Neurosci Biobehav Rev24817842
- 124. Ridgway S, Houser D, Finneran J, Carder D, Keogh M, et al. (2006) Functional imaging of dolphin brain metabolism and blood flow. J Exp Biol 209: 2902–2910.S. RidgwayD. HouserJ. FinneranD. CarderM. Keogh2006Functional imaging of dolphin brain metabolism and blood flow.J Exp Biol20929022910
- 125. Ridgway S, Carder D, Finneran J, Keogh M, Kamolnick T, et al. (2006) Dolphin continuous auditory vigilance for five days. J Exp Biol 209: 3621–3628.S. RidgwayD. CarderJ. FinneranM. KeoghT. Kamolnick2006Dolphin continuous auditory vigilance for five days.J Exp Biol20936213628
- 126. Lyamin O, Pryaslova J, Lance V, Siegel J (2005) Animal behaviour: continuous activity in cetaceans after birth. Nature 435: 1177.O. LyaminJ. PryaslovaV. LanceJ. Siegel2005Animal behaviour: continuous activity in cetaceans after birth.Nature4351177
- 127. Gnone G, Moriconi T, Gambini G (2006) Sleep behaviour: activity and sleep in dolphins. Nature 441: E10–11.G. GnoneT. MoriconiG. Gambini2006Sleep behaviour: activity and sleep in dolphins.Nature441E1011
- 128. Sekiguchi Y, Arai K, Kohshima S (2006) Sleep behaviour: sleep in continuously active dolphins. Nature 441: E9–10.Y. SekiguchiK. AraiS. Kohshima2006Sleep behaviour: sleep in continuously active dolphins.Nature441E910