The Reason for Sleep in Animal Life

Trends in Neurosciences, 2008

The past ten years have seen new approaches to elucidating genetic pathways regulating sleep. The emerging theme is that sleep-like states are conserved in evolution, with similar signaling pathways playing a role in animals as distantly related as flies and humans. We review the evidence for the presence of sleep states in non-mammalian species including zebrafish (Danio rerio), fruit flies (Drosophila melanogaster), and round worms (Caenorhabditis elegans). We describe conserved sleep-regulatory molecular pathways with a focus on cAMP and Epidermal Growth Factor (EGF) signaling; neurotransmitters with conserved effects on sleep and wake regulation, including dopamine and GABA; and a conserved molecular response to sleep deprivation involving the chaperone protein BiP/GRP78.

Nature, 2005

The functions of mammalian sleep remain unclear. Most theories suggest a role for non-rapid eye movement (NREM) sleep in energy conservation and in nervous system recuperation. Theories of REM sleep have suggested a role for this state in periodic brain activation during sleep, in localized recuperative processes and in emotional regulation. Across mammals, the amount and nature of sleep are correlated with age, body size and ecological variables, such as whether the animals live in a terrestrial or an aquatic environment, their diet and the safety of their sleeping site. Sleep may be an efficient time for the completion of a number of functions, but variations in sleep expression indicate that these functions may differ across species. Saying that it is desirable to be well rested and that the body seeks lost sleep with a vigour comparable to or greater than that displayed for food or sex does not answer the question of the functional role of sleep. Why do we spend one-third of our lives asleep? Why has our body evolved to press us relentlessly to make up for lost sleep? Can we separate the drive for sleep, manifested in sleepiness, from the function of sleep, as we can separate hunger from the benefits of food consumption? Why do so many species habitually sleep much more than humans, and others much less, and how do species that sleep for only short periods accomplish the functions of sleep in less time? Why does the daily sleep amount decrease from birth to maturity in all species of terrestrial mammals? And why do we have two kinds of sleep, rapid eye movement (REM) and non-REM (NREM) sleep? Sleep can be defined as a state of immobility with greatly reduced responsiveness, which can be distinguished from coma or anaesthesia by its rapid reversibility. An additional defining characteristic of sleep is that when it is prevented, the body tries to recover the lost amount. The existence of sleep 'rebound' after deprivation 1 demonstrates that sleep is not simply a period of reduced activity or alertness regulated by circadian or ultradian rhythms, a phenomenon that can be seen even in non-sleeping organisms 2-4. The amplitude of the changes in brain metabolism and neuronal activity that occurs during sleep exceeds those which occur during most waking periods 5-7. The argument that sleep serves a vital function is compelling. Sleep deprivation in rodents and flies can cause death more quickly than food deprivation 8. Nevertheless, we must not assume that the effects of sleep loss are independent of the deprivation technique used or that sleep loss has equally dire effects in all animals 9,10. In this review we will consider the vast knowledge that has been gained about the physiological nature of sleep and sleep-control mechanisms, evidence from sleep-deprivation studies and the distribution of sleep across species in the context of theories of sleep function. These data support theories that suggest that sleep saves energy, keeps species from being active at inopportune times and reverses wakinginduced changes in brain function. The evidence suggests distinct roles for REM and NREM sleep. It is also clear that sleep expression is adapted to ecological factors and may differ qualitatively across species. Sleep-controlling brain regions in mammals Neurophysiological studies have provided considerable information about the mechanisms controlling sleep states. These data can guide theories of sleep functions. Detailed reviews of the physiological control of sleep are available elsewhere 11 , but for the purposes of the current review, several aspects will be highlighted. NREM sleep phenomena can be generated by the isolated forebrain 12-14. Groups of sleep-active neurons have been discovered in the preoptic and basal forebrain regions (Fig. 1). These cells are maximally active during NREM sleep, and when stimulated will induce this state. Conversely, damage to these regions greatly reduces sleep. These neurons act through direct and indirect inhibitory projections to aminergic, cholinergic and hypocretinergic (also called orexinergic) neurons in the forebrain and brainstem. These and other neuronal groups maintain waking. The preoptic and anterior hypothalamic regions, within which most of these sleep-active neurons are embedded, have central roles in controlling the body and brain's temperature 15. Many sleep-active neurons are thermosensitive; when studied in tissue slices and in the intact brain they increase their activity at higher temperatures 12. Heating of the preoptic regions increases NREM sleep. REM sleep phenomena can be generated by the isolated brainstem,

Progress in Neurobiology, 2000

Simple animal models have allowed biologists to apply the tools of modern molecular genetics to such complex behaviors as circadian rhythms and long-term memory consolidation. The mechanisms and molecules discovered in these simple animals are evolutionarily conserved in other species, including mammals. Sleep research lacks a simple animal model because criteria based on the electroencephalogram have been met only in birds and mammals. We argue that straightforward behavioral criteria could allow the identi®cation of a sleep-like rest state that might be useful for molecular investigations to understand the regulation and function of sleep. Candidate model systems are discussed, leading to the conclusion that several species have complementary strengths. Speci®cally, techniques developed for larval zebra®sh can be used to visualize neural ®ring patterns in the living animal, and the fruit¯y Drosophila melanogaster has been used successfully for molecular and genetic dissection of complex behaviors. We conclude with a hypothesis that one putative function of sleep, the optimization of neural plasticity, would also have adaptive value in simple organisms and might therefore be evolutionarily conserved. #

Brain Research, 1999

Sleep deprivation leads to cognitive impairments in humans and, if sustained for 2-3 weeks in rats, it is invariably fatal. It has been suggested that neural activity associated with waking, if it is not interrupted by periods of sleep, may damage brain cells through excitotoxic or oxidative mechanisms and eventually lead to cell death. To determine whether sustained waking causes brain cell degeneration, three parallel strategies were used. The presence and extent of DNA fragmentation was analyzed with the TUNEL Ž . technique on brain sections from rats sleep deprived for various periods of time from 8 h to 14 days and from their respective controls.

Neuron, 2004

have identified hundreds of transcripts that cycle with circadian time in the brain and peripheral tissues of mice (Akhtar et al., 2002; Panda et al., 2002; Storch et al., 2002; Ueda et al., 2002a) and flies (Claridge-Chang et Summary al., 2001; McDonald and Rosbash, 2001; Ceriani et al., 2002; Lin et al., 2002; Ueda et al., 2002b)

Current Opinion in Physiology, 2020

Sleep is a universal phenomenon occurring in all species studied thus far. Sleep loss results in adverse physiological effects at both the organismal and cellular levels suggesting an adaptive role for sleep in the maintenance of overall health. This review examines the bidirectional relationship between sleep and cellular stress. Cellular stress in this review refers to a shift in cellular homeostasis in response to an external stressor. Studies that illustrate the fact that sleep loss induces cellular stress and those that provide evidence that cellular stress in turn promotes sleep will be discussed.

Indian Journal of Sleep Medicine, 2012

T he phenomenon of sleep exists across the animal kingdom. Sleep is an important and critical behavioural state essential for maintaining health and survival. Sleep is defined behaviourally as a physiological state of rapidly reversible period of immobility associated with characteristic posture, reduced motor activity and increased response threshold for external sensory stimulation. During sleep, we do not interact with the external environment and often enters into dream state. Sleep is essential for the adaptation of organism to its environment and thereby important for the growth and survival. Cetaceans such as dolphins execute many functions such as locomotion, thermoregulation and so on while one hemisphere is engaged in sleep like activity. Sleep is thus necessary for proper functioning of the brain and is necessary for the survival of the organism. During the process of evolution,

Physiological …, 2006

Annals of the New York Academy of Sciences, 2008

Major questions on the biology of sleep include the following: what are the molecular functions of sleep; why can wakefulness only be sustained for defined periods before there is behavioral impairment; what genes contribute to the individual differences in sleep and the response to sleep deprivation? Behavioral criteria to define sleep have facilitated identification of sleep states in a number of different model systems: Drosophila, zebrafish, and Caenorhabditis elegans. Each system has unique strengths. Studies in these model systems are identifying conserved signaling mechanisms regulating sleep that are present in mammals. For example, the PKA-CREB signaling mechanism promotes wakefulness in Drosophila, mice, and C.

2007

The function(s) of sleep remains a major unanswered question in biology. We assessed changes in gene expression in the mouse cerebral cortex and hypothalamus following different durations of sleep and periods of sleep deprivation. There were significant differences in gene expression between behavioral states; we identified 3,988 genes in the cerebral cortex and 823 genes in the hypothalamus with altered expression patterns between sleep and sleep deprivation. Changes in the steady-state level of transcripts for various genes are remarkably common during sleep, as 2,090 genes in the cerebral cortex and 409 genes in the hypothalamus were defined as sleep specific and changed (increased or decreased) their expression during sleep. The largest categories of overrepresented genes increasing expression with sleep were those involved in biosynthesis and transport. In both the cerebral cortex and hypothalamus, during sleep there was upregulation of multiple genes encoding various enzymes involved in cholesterol synthesis, as well as proteins for lipid transport. There was also upregulation during sleep of genes involved in synthesis of proteins, heme, and maintenance of vesicle pools, as well as antioxidant enzymes and genes encoding proteins of energy-regulating pathways. We postulate that during sleep there is a rebuilding of multiple key cellular components in preparation for subsequent wakefulness. MATERIALS AND METHODS Animal Handling Experiments were performed on male mice (C57BL/6J) 10 wk of age Ϯ 1 wk. Animals were housed in a light/dark cycle of 12 h, in a pathogen-free, temperature-and humidity-controlled room (22°C and 45-55%, respectively) with water available ad libitum. Food was accessible for 12 h only during the active period (15). Animals were subjected to 14 days of acclimatization during which a nighttime feeding pattern was established. This was done to avoid differential food intake between mice that were subsequently sleep deprived during the lights-on period and those allowed to sleep. During the acclimatization process, all animals were given time to become accustomed to the extended presence of an experimenter, repeated gentle touching, and presence in the cage of such objects as fragments Article published online before print. See web site for date of publication (http://physiolgenomics.physiology.org).