Mammalian Sleep Research Articles

Central pattern generator control of a vertebrate ultradian sleep rhythm.

The mechanisms underlying the mammalian ultradian sleep rhythm-the alternation of rapid-eye-movement (REM) and slow-wave (SW) states-are not well understood but probably depend, at least in part, on circuits in the brainstem1-6. Here, we use perturbation experiments to probe this ultradian rhythm in sleeping lizards (Pogona vitticeps)7-9 and test the hypothesis that it originates in a central pattern generator10,11-circuits that are typically susceptible to phase-dependent reset and entrainment by external stimuli12. Using light pulses, we find that Pogona's ultradian rhythm8 can be reset in a phase-dependent manner, with a critical transition from phase delay to phase advance in the middle of SW. The ultradian rhythm frequency can be decreased or increased, within limits, by entrainment with light pulses. During entrainment, Pogona REM (REMP)can be shortened but not lengthened, whereas SW can be dilated more flexibly. In awake animals, a few alternating light/dark epochs matching natural REMP and SW durations entrain a sleep-like brain rhythm, suggesting the transient activation of an ultradian rhythm generator. In sleeping animals, a light pulse delivered to a single eye causes an immediate ultradian rhythm reset, but only of the contralateral hemisphere; both sides resynchronize spontaneously, indicating that sleep is controlled by paired rhythm-generating circuits linked by functional excitation. Our results indicate that central pattern generators of a type usually known to control motor rhythms may also organize the ultradian sleep rhythm in a vertebrate.

Sedative Effects of Daidzin, Possibly Through the GABAA Receptor Interaction Pathway: In Vivo Approach with Molecular Dynamic Simulations.

The soy isoflavone daidzin (DZN) has been considered a hopeful bioactive compound having diverse biological activities, including anxiolytic, memory-enhancing, and antiepileptic effects, in experimental animals. However, its sedative and hypnotic effects are yet to be discovered. This study aimed to evaluate its sedative/hypnotic effect on Swiss mice. Additionally, in silico studies were also performed to see the possible molecular mechanisms behind the tested neurological effect. For this, male Swiss albino mice were treated with DZN (5, 10, or 20mg/kg) intraperitoneally (i.p.) with or without the standard GABAergic medication diazepam(DZP) and/or flumazenil(FLU) and checked for the onset and duration of sleeping time using thiopental sodium-induced as well as DZP-induced sleeping tests. A molecular docking study was also performed to check its interaction capacity with the α1 and β2 subunits of the GABAA receptor. Findings suggest that DZN dose-dependently and significantly reduced the latency while increasing the duration of sleep in animals. In combination therapy, DZN shows synergistic effects with the DZP-2 and DZP-2 + FLU-0.01 groups, resulting in significantly (p < 0.05) reduced latency and increased sleep duration. Further, molecular docking studies demonstrate that DZN has a strong binding affinity of - 7.2kcal/mol, which is closer to the standard ligand DZP (- 8.3kcal/mol) against the GABAA (6X3X) receptor. Molecular dynamic simulations indicated stability and similar binding locations for DZP and DZN with 6X3X. In conclusion, DZN shows sedative effects on Swiss mice, possibly through the GABAA receptor interaction pathway.

Comparison of rhythmic jaw muscle activities induced by electrical stimulations of the corticobulbar tract during rapid eye movement sleep with those during wakefulness and non-rapid eye movement sleep in freely moving Guinea pigs

ObjectiveRhythmic jaw muscle activities (RJMAs) occur during rapid eye movement (REM) sleep in humans and animals even though motoneurons are inhibited. The present study compared the characteristics of jaw muscle activities induced by electrical microstimulations of the corticobulbar tract (CT) during REM sleep with those during wakefulness and non-REM sleep. MethodsEleven guinea pigs were surgically prepared for polygraphic recordings with the implantation of a stimulating electrode. Long- and short-train repetitive electrical microstimulations were applied to the CT under freely moving conditions. The response rate, latency, burst amplitude, and cycle length in the digastric muscle were calculated and cortical and cardiac activities were quantified. ResultsLong-train microstimulations induced RJMAs in the digastric muscle followed by masseter muscle activity during wakefulness and non-REM sleep and only induced rhythmic digastric muscle activity during REM sleep. The response rate of RJMAs and the burst amplitude of digastric muscles were significantly lower during REM sleep than during wakefulness and non-REM sleep. However, response latency did not significantly differ between REM sleep and wakefulness. Transient cortical and cardiac changes were associated with RJMAs induced during non-REM sleep, but not during REM sleep. Short-train microstimulations induced a short-latency digastric response, the amplitude of which was significantly lower during REM sleep than during non-REM sleep and wakefulness. ConclusionsThese results suggest that the masticatory CPG was activated by electrical CT stimulations independently of the motoneuron inhibitory system during REM sleep.

Cyclooxygenase-2 (COX-2)-dependent mechanisms mediate sleep responses to microbial and thermal stimuli

Prostaglandins (PGs) play a crucial role in sleep regulation, yet the broader physiological context that leads to the activation of the prostaglandin-mediated sleep-promoting system remains elusive. In this study, we explored sleep-inducing mechanisms potentially involving PGs, including microbial, immune and thermal stimuli as well as homeostatic sleep responses induced by short-term sleep deprivation using cyclooxygenase-2 knockout (COX-2 KO) mice and their wild-type littermates (WT). Systemic administration of 0.4 µg lipopolysaccharide (LPS) induced increased non-rapid-eye movement sleep (NREMS) and fever in WT animals, these effects were completely absent in COX-2 KO mice. This finding underscores the essential role of COX-2-dependent prostaglandins in mediating sleep and febrile responses to LPS. In contrast, the sleep and fever responses induced by tumor necrosis factor α, a proinflammatory cytokine which activates COX-2, were preserved in COX-2 KO animals, indicating that these effects are independent of COX-2-related signaling. Additionally, we examined the impact of ambient temperature on sleep. The sleep-promoting effects of moderate warm ambient temperature were suppressed in COX-2 KO animals, resulting in significantly reduced NREMS at ambient temperatures of 30 °C and 35 °C compared to WT mice. However, rapid-eye-movement sleep responses to moderately cold or warm temperatures did not differ between the two genotypes. Furthermore, 6 h of sleep deprivation induced rebound increases in sleep with no significant differences observed between COX-2 KO and WT mice. This suggests that while COX-2-derived prostaglandins are crucial for the somnogenic effects of increased ambient temperature, the homeostatic responses to sleep loss are COX-2-independent. Overall, the results highlight the critical role of COX-2-derived prostaglandins as mediators of the sleep-wake and thermoregulatory responses to various physiological challenges, including microbial, immune, and thermal stimuli. These findings emphasize the interconnected regulation of body temperature and sleep, with peripheral mechanisms emerging as key players in these integrative processes.

Energy Deficit is a Key Driver of Sleep Homeostasis.

Sleep and feeding are vital homeostatic behaviors, and disruptions in either can result in substantial metabolic consequences. Distinct neuronal manipulations in Drosophila can dissociate sleep loss from subsequent homeostatic rebound, offering an optimal platform to examine the precise interplay between these fundamental behaviors. Here, we investigate concomitant changes in sleep and food intake in individual animals, as well as respiratory metabolic expenditure, that accompany behavioral and genetic manipulations that induce sleep loss in Drosophila melanogaster. We find that sleep disruptions resulting in energy deficit through increased metabolic expenditure and manifested as increased food intake were consistently followed by rebound sleep. In contrast, "soft" sleep loss, which does not induce rebound sleep, is not accompanied by increased metabolism and food intake. Our results demonstrate that homeostatic sleep rebound is linked to energy deficit accrued during sleep loss. Collectively, these findings support the notion that sleep functions to conserve energy and highlight the need to examine the effects of metabolic therapeutics on sleep.

Melatonin: The Multifaceted Molecule in Plant Growth and Defense.

Melatonin (MEL), a hormone primarily known for its role in regulating sleep and circadian rhythms in animals, has emerged as a multifaceted molecule in plants. Recent research has shed light on its diverse functions in plant growth and defense mechanisms. This review explores the intricate roles of MEL in plant growth and defense responses. MEL is involved in plant growth owing to its influence on hormone regulation. MEL promotes root elongation and lateral root formation and enhances photosynthesis, thereby promoting overall plant growth and productivity. Additionally, MEL is implicated in regulating the circadian rhythm of plants, affecting key physiological processes that influence plant growth patterns. MEL also exhibits antioxidant properties and scavenges reactive oxygen species, thereby mitigating oxidative stress. Furthermore, it activates defense pathways against various biotic stressors. MEL also enhances the production of secondary metabolites that contribute to plant resistance against environmental changes. MEL's ability to modulate plant response to abiotic stresses has also been extensively studied. It regulates stomatal closure, conserves water, and enhances stress tolerance by activating stress-responsive genes and modulating signaling pathways. Moreover, MEL and nitric oxide cooperate in stress responses, antioxidant defense, and plant growth. Understanding the mechanisms underlying MEL's actions in plants will provide new insights into the development of innovative strategies for enhancing crop productivity, improving stress tolerance, and combating plant diseases. Further research in this area will deepen our knowledge of MEL's intricate functions and its potential applications in sustainable agriculture.

Sleep in the wild: the importance of individual effects and environmental conditions on sleep behaviour in wild boar.

Sleep serves vital physiological functions, yet how sleep in wild animals is influenced by environmental conditions is poorly understood. Here we use high-resolution biologgers to investigate sleep in wild animals over ecologically relevant time scales and quantify variability between individuals under changing conditions. We developed a robust classification for accelerometer data and measured multiple dimensions of sleep in the wild boar (Sus scrofa) over an annual cycle. In support of the hypothesis that environmental conditions determine thermoregulatory challenges, which regulate sleep, we show that sleep quantity, efficiency and quality are reduced on warmer days, sleep is less fragmented in longer and more humid days, while greater snow cover and rainfall promote sleep quality. Importantly, this longest and most detailed analysis of sleep in wild animals to date reveals large inter- and intra-individual variation. Specifically, short-sleepers sleep up to 46% less than long-sleepers but do not compensate for their short sleep through greater plasticity or quality, suggesting they may pay higher costs of sleep deprivation. Given the major role of sleep in health, our results suggest that global warming and the associated increase in extreme climatic events are likely to negatively impact sleep, and consequently health, in wildlife, particularly in nocturnal animals.

Sleep and Thermoregulation in Birds: Cold Exposure Reduces Brain Temperature but Has Little Influence on Sleep Time and Sleep Architecture in Jackdaws (Coloeus monedula).

Birds have an electrophysiological sleep state that resembles mammalian rapid-eye-movement (REM) sleep. However, whether its regulation and function are similar is unclear. In the current experiment, we studied REM sleep regulation in jackdaws (Coloeus monedula) by exposing the birds to low ambient temperature, a procedure that selectively suppresses REM sleep in mammals. Eight jackdaws were equipped with electrodes to record brain activity and neck muscle activity and a thermistor to record cortical brain temperature. Recordings covered a three-day period starting with a 24 h baseline day at an ambient temperature of 21 °C, followed by a 12 h cold night at 4 °C, after which the ambient temperature was restored to 21 °C for the remaining recovery period. Cold exposure at night caused a significant drop in brain temperature of 1.4 °C compared to the baseline night. However, throughout the cold night, jackdaws expressed NREM sleep and REM sleep levels that were not significantly different from the baseline. Also, EEG spectral power during NREM sleep was unaffected by cold exposure. Thus, while cold exposure had a clear effect on brain temperature in jackdaws, it did not have the same REM sleep suppressing effect reported for mammals. These findings suggest that the REM-sleep-like state in birds, unlike REM sleep in mammals, is protected against the influence of low temperature.

Digitalization of toxicology: improving preclinical to clinical translation.

Though the portfolio of medicines that are extending and improving the lives of patients continues to grow, drug discovery and development remains a challenging business on its best day. Safety liabilities are a significant contributor to development attrition where the costliest liabilities to both drug developers and patients emerge in late development or post-marketing. Animal studies are an important and influential contributor to the current drug discovery and development paradigm intending to provide evidence that a novel drug candidate can be used safely and effectively in human volunteers and patients. However, translational gaps-such as toxicity in patients not predicted by animal studies-have prompted efforts to improve their effectiveness, especially in safety assessment. More holistic monitoring and "digitalization" of animal studies has the potential to enrich study outcomes leading to datasets that are more computationally accessible, translationally relevant, replicable, and technically efficient. Continuous monitoring of animal behavior and physiology enables longitudinal assessment of drug effects, detection of effects during the animal's sleep and wake cycles and the opportunity to detect health or welfare events earlier. Automated measures can also mitigate human biases and reduce subjectivity. Reinventing a conservative, standardized, and traditional paradigm like drug safety assessment requires the collaboration and contributions of a broad and multi-disciplinary stakeholder group. In this perspective, we review the current state of the field and discuss opportunities to improve current approaches by more fully leveraging the power of sensor technologies, artificial intelligence (AI), and animal behavior in a home cage environment.

Phytochemical, Pharmacological, and Molecular Docking Study of Dry Extracts of Matricaria discoidea DC. with Analgesic and Soporific Activities.

Pineapple weed (Matricaria discoidea DC.) is a widespread plant in Europe and North America. In ethnomedicine, it is well-known for its anti-inflammatory and spasmolytic activities. The aim of this research was to develop novel methods of M. discoidea processing to obtain essential oil and dry extracts and to investigate their phytochemical compositions. Moreover, the molecular docking of the main substances and the in vivo studies on their soporific and analgesic activities were conducted. The essential oil and two dry extracts from M. discoidea were prepared. A total of 16 phenolic compounds (seven flavonoids, seven hydroxycinnamic acids, and two phenolic acids) in the dry extracts were identified by means of UPLC-MS/MS. In the essential oil, nine main terpenoids were identified by gas chromatography (GC). It was shown that phenolic extraction from the herb was successful when using 70% ethanol in a triple extraction method and at a ratio of 1:14-1:16. The in vivo studies with rodents demonstrated the analgesic activity of the M. discoidea extracts and improvements in the sleep of animals. The dry extracts of M. discoidea did not show any toxicity. The molecular docking analysis showed a high probability of COX-1,2 inhibition and NMDA receptor antagonism by the extracts.

Crucial role of TFAP2B in the nervous system for regulating NREM sleep.

The AP-2 transcription factors are crucial for regulating sleep in both vertebrate and invertebrate animals. In mice, loss of function of the transcription factor AP-2β (TFAP2B) reduces non-rapid eye movement (NREM) sleep. When and where TFAP2B functions, however, is unclear. Here, we used the Cre-loxP system to generate mice in which Tfap2b was specifically deleted in the nervous system during development and mice in which neuronal Tfap2b was specifically deleted postnatally. Both types of mice exhibited reduced NREM sleep, but the nervous system-specific deletion of Tfap2b resulted in more severe sleep phenotypes accompanied by defective light entrainment of the circadian clock and stereotypic jumping behavior. These findings indicate that TFAP2B in postnatal neurons functions at least partly in sleep regulation and imply that TFAP2B also functions either at earlier stages or in additional cell types within the nervous system.

Adaptive changes in BMAL2 with increased locomotion associated with the evolution of unihemispheric slow-wave sleep in mammals.

Marine mammals, especially cetaceans, have evolved a very special form of sleep characterized by unihemispheric slow-wave sleep (USWS) and a negligible amount or complete absence of rapid-eye-movement sleep; however, the underlying genetic mechanisms remain unclear. Here, we detected unique, significant selection signatures in basic helix-loop-helix ARNT like 2 (BMAL2; also called ARNTL2), a key circadian regulator, in marine mammal lineages, and identified two nonsynonymous amino acid substitutions (K204E and K346Q) in the important PER-ARNT-SIM domain of cetacean BMAL2 via sequence comparison with other mammals. In vitro assays revealed that these cetacean-specific mutations specifically enhanced the response to E-box-like enhancer and consequently promoted the transcriptional activation of PER2, which is closely linked to sleep regulation. The increased PER2 expression, which was further confirmed both in vitro and in vivo, is beneficial for allowing cetaceans to maintain continuous movement and alertness during sleep. Concordantly, the locomotor activities of zebrafish overexpressing the cetacean-specific mutant bmal2 were significantly higher than the zebrafish overexpressing the wild-type gene. Subsequently, transcriptome analyses revealed that cetacean-specific mutations caused the upregulation of arousal-related genes and the downregulation of several sleep-promoting genes, which is consistent with the need to maintain hemispheric arousal during USWS. Our findings suggest a potential close relationship between adaptive changes in BMAL2 and the remarkable adaptation of USWS and may provide novel insights into the genetic basis of the evolution of animal sleep.

Noninvasive EEG measurement of sleep in the family cat and comparison with the dog

Abstract We have successfully measured the sleep electroencephalogram (EEG) of 12 family cats during an afternoon nap using a completely noninvasive methodology originally developed and validated for family dogs. Extracting both macrostructural and spectral sleep variables from the acquired data, we: (1) provided a descriptive analysis of sleep structure in cats and the power spectral density (PSD) distribution considering 3 sleep stages—drowsiness, non-rapid eye movement (NREM), and rapid eye movement (REM) sleep; and (2) compared the results to those obtained in family dogs measured under the same conditions and using the same methodology. Importantly, our description of sleep structure and PSD distribution in cats proved to be comparable to those of earlier invasive studies, highlighting that appropriate noninvasive methodologies may provide a viable alternative to those that are invasive in some cases. While no macrostructural differences were found between the sleep of cats and dogs, and the characteristic PSDs were mostly similar across sleep stages within the 2 species, the high-frequency resolution comparison of PSD distributions revealed differences between the 2 species in all sleep stages (concerning the delta, theta, alpha, sigma, and beta bands in drowsiness and NREM sleep; and the delta, alpha, and sigma bands in REM sleep). Potential factors underlying these differences are discussed, including differences in circadian rhythms, sleep homeostatic regulation, experienced stress, or even differential attitudes toward owners—highlighting important links between sleep characteristics and often more complex neural and behavioral features.

Beacon-based sleep-wake monitoring in dogs.

The sleep-wake cycle represents a crucial physiological process essential for maintaining homeostasis and promoting individual growth. In dogs, alterations in sleep patterns associated with age and dog's correlation with temperament factors, such as nervousness, have been reported, and there is an increasing demand for precise monitoring of sleep and physical activity in dogs. The present study aims to develop an analysis method for measuring sleep-wake patterns and physical activity in dogs by utilizing an accelerometer and a smartphone. By analyzing time series data collected from the accelerometer attached to the dog's collar, a comprehensive sleep and activity analysis model was constructed. This model classified the activity level into seven classes and effectively highlighted the variations in sleep-activity patterns. Two classes with lower activity levels were considered as sleep, while other five levels were regarded as wake based on the rate of occurrence. This protocol of data acquisition and analysis provides a methodology that enables accurate and extended evaluation of both sleep and physical activity in dogs.

Research on genetic regulation of sleep

Sleep is the most vital function of mammals to maintain energy homeostasis. For years, the mechanism behind how sleep is regulated has been studied, and several genetic pathways had been identified as the key to encoding the circadian rhythms to enable the mammalian sleep and wake cycles. This paper explains the mechanisms behind the PER, CRY, CLOCK, and BMAL1 pathways, which play a central role in manipulating the function of the circadian clock. Other pathways, such as the DEC1/2 genes, interact with the circadian clock genes to form negative feedback loops to further control the circadian rhythm pathway and directly regulate sleep through orexin. Mutations occurring in these pathways could potentially cause conditions such as narcolepsy, restless leg syndrome, insomnia, sleep apnea, delayed sleep phase syndrome (DSPS), and advanced sleep phase syndrome (ASPS). These conclusions are based on previous studies and experiments that identified these pathways. While recent studies have shed light on the mechanisms of the PER, CLOCK, BMAL1, and DEC genes in regulating sleep and circadian rhythms, there is still much to discover. The intricate interactions and genetic pathways involved in sleep regulation are not yet fully understood. Further research in this field may uncover new insights into the genetic basis of sleep and provide avenues for developing interventions to address sleep disorders.

Comparative Analysis of REM and NREM Sleep in Mammals, Reptiles, and Cephalopoda with Relations to Dreaming

Comparative Analysis of REM and NREM Sleep in Mammals, Reptiles, and Cephalopoda with Relations to Dreaming

Experimentally induced active and quiet sleep engage non-overlapping transcriptional programs in Drosophila

Sleep in mammals can be broadly classified into two different physiological categories: rapid eye movement (REM) sleep and slow-wave sleep (SWS), and accordingly REM and SWS are thought to achieve a different set of functions. The fruit fly Drosophila melanogaster is increasingly being used as a model to understand sleep functions, although it remains unclear if the fly brain also engages in different kinds of sleep as well. Here, we compare two commonly used approaches for studying sleep experimentally in Drosophila: optogenetic activation of sleep-promoting neurons and provision of a sleep-promoting drug, gaboxadol. We find that these different sleep-induction methods have similar effects on increasing sleep duration, but divergent effects on brain activity. Transcriptomic analysis reveals that drug-induced deep sleep (‘quiet’ sleep) mostly downregulates metabolism genes, whereas optogenetic ‘active’ sleep upregulates a wide range of genes relevant to normal waking functions. This suggests that optogenetics and pharmacological induction of sleep in Drosophila promote different features of sleep, which engage different sets of genes to achieve their respective functions.

Experimentally induced active and quiet sleep engage non-overlapping transcriptional programs in Drosophila.

Sleep in mammals can be broadly classified into two different physiological categories: rapid eye movement (REM) sleep and slow-wave sleep (SWS), and accordingly REM and SWS are thought to achieve a different set of functions. The fruit fly Drosophila melanogaster is increasingly being used as a model to understand sleep functions, although it remains unclear if the fly brain also engages in different kinds of sleep as well. Here, we compare two commonly used approaches for studying sleep experimentally in Drosophila: optogenetic activation of sleep-promoting neurons and provision of a sleep-promoting drug, gaboxadol. We find that these different sleep-induction methods have similar effects on increasing sleep duration, but divergent effects on brain activity. Transcriptomic analysis reveals that drug-induced deep sleep ('quiet' sleep) mostly downregulates metabolism genes, whereas optogenetic 'active' sleep upregulates a wide range of genes relevant to normal waking functions. This suggests that optogenetics and pharmacological induction of sleep in Drosophila promote different features of sleep, which engage different sets of genes to achieve their respective functions.

A Preliminary Analysis of Psychiatric Service Dog Placements and Sleep Patterns of Partners of Veterans With PTSD

ABSTRACT Partners of veterans diagnosed with posttraumatic stress disorder (PTSD) are at risk of a variety of challenges, and it is unknown whether psychiatric service dogs are disruptive to their sleep or provide similar benefits that are seen in the limited literature on veterans. As part of a larger clinical trial examining the efficacy of psychiatric service dogs for veterans with PTSD and their families, this study focused on sleep patterns of veterans’ partners (n = 88), incorporating both subjective (clinically validated self-report surveys) and objective sleep measures (actigraphy). Linear regression was used to analyze differences in relation to group (intervention versus control) at follow-up, controlling for baseline score. Results revealed no significant differences between groups for both the subjective surveys (p = 0.15; p = 0.75) and the objective actigraphy measures (p = 0.06–0.98). This suggests that psychiatric service dogs are not disruptive, nor do they provide any benefits to partner sleep. Partners had sleep patterns on par with national norms at baseline and remained at such levels at follow up. Ultimately, using both subjective and objective measures, we found no impact of psychiatric service dogs on the sleep of veterans’ partners. Trial registration: ClinicalTrials.gov identifier: NCT03245814.

P054 Neurotransmitters of Sleep and Wake in Flatworms

Abstract Introduction Sleep is something that we all do, regardless of how much or how little. But why we sleep, and how sleep evolved is still something of a mystery. This research investigated how neurotransmitters and pharmaceuticals commonly seen in mammalian sleep and wake, play a role in the sleep of free-living flatworms. Methods Using behavioural methods, I observed the behaviour of flatworms under a 12:12 LD lighting condition. Using seven neurotransmitters and one pharmaceutical, I used a novel “yolk and soak” method – feeding the animals the neurotransmitter via hard-boiled egg yolk, as well as bathing them in the same concentration of neurotransmitter, to modulate their behaviour to either induce sleep, or wakefulness. Results We found that GABA, dopamine and histamine appear to be evolutionarily conserved. By dosing the flatworms with these neurotransmitters, we saw that the behaviour changed toward sleep (GABA) or wakefulness (dopamine and histamine) as it does in more recently evolved mammals. We also saw that the H1 antagonist Pyrilamine induced sleep, as it does in other animals. Discussion Understanding how neurotransmitters involved in sleep and wake in humans, and other mammals, may work in animals that are neurologically simple, and older in evolution can lead to many opportunities. We now know that GABA, dopamine and histamine promote sleep and wake in animals that have lost most of their complex systems through secondary simplification, suggesting that these neurotransmitters might be key to the origin of sleep, and may help to understand sleep disorders in humans.