Homeostatic Regulation Of Sleep Research Articles

Local sleep in songbirds: different simultaneous sleep states across the avian pallium.

Wakefulness and sleep have often been treated as distinct and global brain states. However, an emerging body of evidence on the local regulation of sleep stages challenges this conventional view. Apart from unihemispheric sleep, the current data that support local variations of neural oscillations during sleep are focused on the homeostatic regulation of local sleep, i.e., the role preceding awake activity. Here, to examine local differences in brain activity during natural sleep, we recorded the electroencephalogram and the local field potential across multiple sites within the avian pallium of zebra finches without perturbing the previous awake state. We scored the sleep stages independently in each pallial site and found that the sleep stages are not pallium-wide phenomena but rather deviate widely across electrode sites. Importantly, deeper electrode sites had a dominant role in defining the temporal aspects of sleep state congruence. Altogether, these findings show that local regulation of sleep oscillations also occurs in the avian brain without prior awake recruitment of specific pallial circuits and in the absence of mammalian cortical neural architecture.

Melatonin, Melatonin Receptors and Sleep: Moving Beyond Traditional Views.

Sleep, constituting approximately one-third of the human lifespan, is a crucial physiological process essential for physical and mental well-being. Normal sleep consists of an orderly progression through wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, all of which are tightly regulated. Melatonin, often referred to as the "hormone of sleep," plays a pivotal role as a regulator of the sleep/wake cycle and exerts its effects through high-affinity G-protein coupled receptors known as MT1 and MT2. Selective modulation of these receptors presents a promising therapeutic avenue for sleep disorders. This review examines research on the multifaceted role of melatonin in sleep regulation, focusing on selective ligands targeting MT1 and MT2 receptors, as well as studies involving MT1 and MT2 knockout mice. Contrary to common beliefs, growing evidence suggests that melatonin, through MT1 and MT2 receptors, might not only influence circadian aspects of sleep but likely, also modulate the homeostatic process of sleep and sleep architecture, or could be the molecule linking the homeostatic and circadian regulation of sleep. Furthermore, the distinct brain localization of MT1 and MT2 receptors, with MT1 receptors primarily regulating REM sleep and MT2 receptors regulating NREM sleep, is discussed. Collectively, sleep regulation extends beyond the circulating levels and circadian peak of melatonin; it also critically involves the expression, molecular activation, and regulatory functions of MT1 and MT2 receptors across various brain regions and nuclei involved in the regulation of sleep. This research underscores the importance of ongoing investigation into the selective roles of MT1 and MT2 receptors in sleep. Such research efforts are expected to pave the way for the development of targeted MT1 or MT2 receptors ligands, thereby optimizing therapeutic interventions for sleep disorders.

Weekday and weekend sleep times across the human lifespan: a model-based simulation.

The shifts in the opposite directions, toward later and earlier sleep timing, occur during the transition through adolescence and adulthood, respectively. Such a n-shape of age-associated change in sleep timing does not resemble the inverse relationship of sleep duration with ages. Age-associated variation in the parameters of the mechanisms of circadian and homeostatic regulation of sleep would underlie these different shapes of relationship of sleep times with ages. Here, we searched for a parsimonious explanation of these different shapes by simulating sleep times on weekdays and weekends with one of the variants of the two-process model of sleep regulation. Using mean age of a sample with reported sleep times on weekdays and weekends, the whole set of 1404 such samples was subdivided into 15 age subsets. Simulations of sleep times in these subsets were performed with and without the suggestion of age-associated variation in the circadian phase. Simulations showed that the age-associated decay of slow-wave activity can parsimoniously explain not only the parallel decreases in weekend sleep duration and rate of the buildup of sleep pressure during the wake phase of the sleep-wake cycle, but also both the delay and advance of sleep timing during the transition through adolescence and adulthood, respectively. The almost functional relationships were revealed between the age-related changes in sleep duration, rate of the buildup of sleep pressure, and slow-wave activity that is a good electrophysiological marker of cortical metabolic rate and synaptic density, strength and efficacy.

Cortical parvalbumin neurons are responsible for homeostatic sleep rebound through CaMKII activation

The homeostatic regulation of sleep is characterized by rebound sleep after prolonged wakefulness, but the molecular and cellular mechanisms underlying this regulation are still unknown. In this study, we show that Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent activity control of parvalbumin (PV)-expressing cortical neurons is involved in homeostatic regulation of sleep in male mice. Prolonged wakefulness enhances cortical PV-neuron activity. Chemogenetic suppression or activation of cortical PV neurons inhibits or induces rebound sleep, implying that rebound sleep is dependent on increased activity of cortical PV neurons. Furthermore, we discovered that CaMKII kinase activity boosts the activity of cortical PV neurons, and that kinase activity is important for homeostatic sleep rebound. Here, we propose that CaMKII-dependent PV-neuron activity represents negative feedback inhibition of cortical neural excitability, which serves as the distributive cortical circuits for sleep homeostatic regulation.

Homeostatic regulation of rapid eye movement sleep by the preoptic area of the hypothalamus

Rapid eye movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POAGAD2→TMN neurons) are crucial for the homeostatic regulation of REMs in mice. POAGAD2→TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POAGAD2→TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POAGAD2→TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.

Homeostatic regulation of rapid eye movement sleep by the preoptic area of the hypothalamus

Rapid eye movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POAGAD2→TMN neurons) are crucial for the homeostatic regulation of REMs in mice. POAGAD2→TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POAGAD2→TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POAGAD2→TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.

The effect of slow wave sleep deprivation on mood in adolescents with depressive symptoms: A pilot study

BackgroundThere is an urgent need for safe, rapid-acting treatment strategies for adolescent depression. In depressed adults, slow wave sleep deprivation (SWSD) improved next-day mood without disrupting sleep duration, but SWSD has not been tested in adolescents. In a pilot study, the aim was to assess the effect of SWSD on sleep physiology and mood outcomes (depression, rumination, anhedonia) among adolescents with depressive symptoms. MethodsSixteen adolescents (17.44 ± 1.46 yr, 12 female) completed three nights of polysomnographic sleep recording: Baseline, SWSD, and Recovery nights. Acoustic stimulation (tones of random pitch, duration, and volume) suppressed slow wave sleep (SWS) in real-time during SWSD. After each night, depression, rumination, and anhedonia severity were assessed. ResultsSWSD successfully suppressed SWS, increased N2, and had minimal impact on Rapid Eye Movement (REM), nocturnal awakenings, and total sleep time. While SWSD did not improve depression or anhedonia severity overall, lower baseline non-REM alpha activity and greater SWS rebound during recovery sleep correlated with SWSD-related reduction in clinician-rated depression severity. Next-day rumination severity decreased after SWSD, with sustained improvements following recovery sleep. However, rumination improvement was not associated with SWS suppression, but rather reduction in total sleep time and REM in exploratory correlation models. LimitationsSmall sample size and large proportion of females. ConclusionSWSD did not improve depression in adolescents overall but a subset with low non-REM alpha activity and intact homeostatic sleep regulation may benefit from this approach. Findings from this pilot study also suggest that partial sleep deprivation may be a beneficial therapeutic strategy for rumination in adolescents.

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.

Sleep disturbance induces a modulation of clock gene expression and alters metabolism regulation in drosophila

Sleep disorders are catching attention worldwide as they can induce dyshomeostasis and health issues in all animals, including humans. Circadian rhythms are biological 24-hour cycles that influence physiology and behavior in all living organisms. Sleep is a crucial resting state for survival and is under the control of circadian rhythms. Studies have shown the influence of sleep on various pathological conditions, including metabolic diseases; however, the biological mechanisms involving the circadian clock, sleep, and metabolism regulation are not well understood. In previous work, we standardized a sleep disturbance protocol and, observed that short-time sleep deprivation and sleep-pattern alteration induce homeostatic sleep regulation, locomotor deficits, and increase oxidative stress. Now, we investigated the relationship between these alterations with the circadian clock and energetic metabolism. In this study, we evaluated the expression of the circadian clock and drosophila insulin-like peptides (DILPs) genes and metabolic markers glucose, triglycerides, and glycogen in fruit flies subjected to short-term sleep disruption protocols. The sleep disturbance altered the expression of clock genes and DILPs genes expression, and modulated glucose, triglycerides, and glycogen levels. Moreover, we demonstrated changes in mTor/dFoxo genes, AKT phosphorylation, and dopamine levels in nocturnal light-exposed flies. Thus, our results suggest a connection between clock genes and metabolism disruption as a consequence of sleep disruption, demonstrating the importance of sleep quality in health maintenance.

Sleep Need, the Key Regulator of Sleep Homeostasis, Is Indicated and Controlled by Phosphorylation of Threonine 221 in Salt Inducible Kinase 3.

Sleep need drives sleep and plays a key role in homeostatic regulation of sleep. So far sleep need can only be inferred by animal behaviors and indicated by electroencephalography (EEG). Here we report that phosphorylation of threonine (T) 221 of the salt inducible kinase 3 (SIK3) increased the catalytic activity and stability of SIK3. T221 phosphorylation in the mouse brain indicates sleep need: more sleep resulting in less phosphorylation and less sleep more phosphorylation during daily sleep/wake cycle and after sleep deprivation (SD). Sleep need was reduced in SIK3 loss of function (LOF) mutants and by T221 mutation to alanine (T221A). Rebound after SD was also decreased in SIK3 LOF and T221A mutant mice. By contrast, SIK1 and SIK2 do not satisfy criteria to be both an indicator and a controller of sleep need. Our results reveal SIK3 T221 phosphorylation as a chemical modification which indicates and controls sleep need.

Earlier Bedtime and Its Effect on Adolescent Sleep Duration.

Sleep duration decreases by ∼10 minutes per year throughout adolescence. A circadian phase delayand changes in homeostatic sleep regulation enable adolescents to stay up later. We determine if teens are able to increase sleep duration by advancing bedtime and whether this ability changes with age. A younger cohort of 77 participants ranging in age from 9.9 to 16.2 years were studied annually for 3 years. An older cohort of 67 participants ranging in age from 15.0 to 20.6 years was studied only once. Annually, participants kept each of 3 different time in bed (TIB) schedules (7, 8.5, and 10 hours) for 4 consecutive nights. Participants kept their habitual weekday rise times; TIB was altered by advancing bedtimes. We report polysomnography-measured sleep durations from the fourth night of the TIB schedule. Despite increases in sleep onset latency and wake after sleep onset, sleep duration increased with TIB as bedtime was advanced. Average (SE) sleep duration increased from 402.8 (1.6) minutes with 7 hours to 470.6 (2.1) minutes with 8.5 hours to 527.5 (3.0) minutes with 10 hours TIB. Sleep duration decreased with age (1.55 [0.48] minutes/year), but the TIB effect on sleep duration did not (TIB by age interaction, P = .42). Adolescents can substantially increase sleep duration by advancing bedtime, and this ability does not change between ages 10 and 21 years. Additional research is needed to determine how to translate these findings from experiment-controlled sleep schedules to real-world sleep duration increases.

Ketamine affects homeostatic sleep regulation in the absence of the circadian sleep-regulating component in freely moving rats

Pharmacological effects of ketamine may affect homeostatic sleep regulation via slow wave related mechanisms.In the present study effects of ketamine applied at anesthetic dose (80 mg/kg) were tested on neocortical electric activity for 24 h in freely moving rats. Ketamine effects were compared to changes during control (saline) injections and after 6 h gentle handling sleep deprivation (SD). As circadian factors may mask drug effects, an illumination protocol consisting of short light-dark cycles was applied.Ketamine application induced a short hypnotic stage with characteristic slow cortical rhythm followed by a long-lasting hyperactive waking resulting pharmacological SD. Coherence analysis indicated an increased level of local synchronization in broad local field potential frequency ranges during hyperactive waking but not during natural- or SD-evoked waking. Both slow wave sleep and rapid eye movement sleep were replaced after the termination of the ketamine effect.Our results show that both ketamine-induced hypnotic state and hyperactive waking can induce homeostatic sleep pressure with comparable intensity as 6 h SD, but ketamine-induced waking was different compared to the SD-evoked one. Both types of waking stages were different compared to spontaneous waking but all three types of wakefulness can engage the homeostatic sleep regulating machinery to generate sleep pressure dissipated by subsequent sleep. Current-source density analysis of the slow waves showed that cortical transmembrane currents were stronger during ketamine-induced hypnotic stage compared to both sleep replacement after SD and ketamine application, but intracortical activation patterns showed only quantitative differences.These findings may hold some translational value for human medical ketamine applications aiming the treatment of depression-associated sleep problems, which can be alleviated by the homeostatic sleep effect of the drug without the need for an intact circadian regulation.

The duration of caffeine treatment plays an essential role in its effect on sleep and circadian rhythm.

Sleep is regulated by the homeostatic system and the circadian clock. Caffeine intake promotes wakefulness in Drosophila. In humans, caffeine is consumed on a daily basis and hence it is important to understand the effect of prolonged caffeine intake on both circadian and homeostatic regulation of sleep. Furthermore, sleep changes with age and the impact of caffeine on age-dependent sleep fragmentation are yet to be understood. Hence in the present study, we examined the effect of short exposure to caffeine on homeostatic sleep and age-dependent sleep fragmentation in Drosophila. We further assessed the effect of prolonged exposure to caffeine on homeostatic sleep and circadian clock. The results of our study showed that short exposure to caffeine reduces sleep and food intake in mature flies. It also enhances sleep fragmentation with increasing age. However, we have not assessed the effect of caffeine on food intake in older flies. On the other hand, prolonged caffeine exposure did not exert any significant effect on the duration of sleep and food intake in mature flies. Nevertheless, prolonged caffeine ingestion decreased the morning and evening anticipatory activity in these flies indicating that it affects the circadian rhythm. These flies also exhibited phase delay in the clock gene timeless transcript oscillation and exhibited either behavioral arrhythmicity or a longer free-running period under constant darkness. In summary, the results of our studies showed that short exposure to caffeine increases the sleep fragmentation with age whereas prolonged caffeine exposure disrupts the circadian clock.

PL-1: DECIPHERING THE MYSTERY OF SLEEP: TOWARD THE MOLECULAR SUBSTRATE FOR SLEEPINESS

Although sleep is a ubiquitous behavior in animal species with central nervous systems, the neurobiology of sleep remain mysterious. Our discovery of orexin, a hypothalamic neuropeptide involved in the maintenance of wakefulness, has helped reveal neural pathways in the regulation of sleep/wakefulness. Orexin receptor antagonists, which specifically block the endogenous waking system, have been approved as a new drug to treat insomnia. Also, since the sleep disorder narcolepsy-cataplexy is caused by orexin deficiency, orexin receptor agonists are expected to provide mechanistic therapy for narcolepsy; they will likely be also useful for treating excessive sleepiness due to other etiologies. Despite the fact that the executive neurocircuitry and neurochemistry for sleep/wake switching has been increasingly revealed in recent years, the mechanism for homeostatic regulation of sleep, as well as the neural substrate for “sleepiness” (sleep need), remains unknown. To crack open this black box, we have initiated a large-scale forward genetic screen of sleep/wake phenotype in mice based on true somnographic (EEG/EMG) measurements. We have so far screened > 10,000 heterozygous ENU-mutagenized founders and established a number of pedigrees exhibiting heritable and specific sleep/wake abnormalities. By combining linkage analysis and the next-generation whole exome sequencing, we have molecularly identified and verified the causal mutations in several of these pedigrees. Biochemical and neurophysiological analyses of these mutations are underway. Indeed, through a systematic cross-comparison of the Sleepy mutants (with a gain-of-function change in a serine/threonine kinase pathway) and sleep-deprived mice, we have found that the cumulative phosphorylation state of a specific set of mostly synaptic proteins may be the molecular substrate of sleep need.

Hyperammonaemia disrupts daily rhythms reversibly by elevating glutamate in the central circadian pacemaker.

Patients with cirrhosis exhibit features of circadian disruption. Hyperammonaemia has been suggested to impair both homeostatic and circadian sleep regulation. Here, we tested if hyperammonaemia directly disrupts circadian rhythm generation in the central pacemaker, the suprachiasmatic nuclei (SCN) of the hypothalamus. Wheel-running activity was recorded from mice fed with a hyperammonaemic or normal diet for ~35 days in a 12:12 light-dark (LD) cycle followed by ~15 days in constant darkness (DD). The expression of the clock protein PERIOD2 (PER2) was recorded from SCN explants before, during and after ammonia exposure, ±glutamate receptor antagonists. In LD, hyperammonaemic mice advanced their daily activity onset time by ~1h (16.8 ± 0.3 vs. 18.1 ± 0.04 h, p=.009) and decreased their total activity, concentrating it during the first half of the night. In DD, hyperammonaemia reduced the amplitude of daily activity (551.5 ± 27.7 vs. 724.9 ± 59 counts, p=.007), with no changes in circadian period. Ammonia (≥0.01 mM) rapidly and significantly reduced PER2 amplitude, and slightly increased circadian period. The decrease in PER2 amplitude correlated with decreased synchrony among circadian cells in the SCN and increased extracellular glutamate, which was rescued by AMPA glutamate receptor antagonists. These data suggest that hyperammonaemia affects circadian regulation of rest-activity behaviour by increasing extracellular glutamate in the SCN.

Dihydropyridine calcium blockers do not interfere with non-rapid eye movement sleep.

Non-rapid eye movement (NREM) sleep is tightly homeostatically regulated and essential for survival. In the electroencephalogram (EEG), oscillations in the delta (0.5-4 Hz) range are prominent during NREM sleep. These delta oscillations are, to date, the best indicator for homeostatic sleep regulation; they are increased after prolonged waking and fade during NREM sleep. The precise mechanisms underlying sleep homeostasis and the generation of EEG delta oscillations are still being investigated. Activity-dependent neuronal calcium influx has been hypothesized to play an important role in generating delta oscillations and might be involved in downstream signaling that mediates sleep function. Dihydropyridine blockers of L-type voltage-gated calcium channels (VGCCs) are in wide clinical use to treat hypertension and other cardiovascular disorders and are readily blood-brain-barrier penetrant. We therefore, wanted to investigate their potential effects on EEG delta oscillation and homeostatic NREM sleep regulation in freely behaving mice. In vivo two-photon imaging of cortical neurons showed larger spontaneous calcium transients in NREM sleep compared to waking. Application of the dihydropyridine calcium blocker nicardipine significantly reduced cortical calcium transients without affecting the generation of delta oscillations. Nicardipine also did not affect EEG delta oscillations over 24 h following application. The time spent in NREM sleep and NREM episode duration was also not affected. Thus, acute block of calcium entry through L-type VGCCs does not interfere with EEG delta oscillations or their homeostatic regulation, despite prior evidence from calcium channel knockout mice.

Sleep need-dependent changes in functional connectivity facilitate transmission of homeostatic sleep drive

How the homeostatic drive for sleep accumulates over time and is released remains poorly understood. In Drosophila, we previously identified the R5 ellipsoid body (EB) neurons as putative sleep drive neurons1 and recently described a mechanism by which astrocytes signal to these cells to convey sleep need.2 Here, we examine the mechanisms acting downstream of the R5 neurons to promote sleep. EM connectome data demonstrate that R5 neurons project to EPG neurons.3 Broad thermogenetic activation of EPG neurons promotes sleep, whereas inhibiting these cells reduces homeostatic sleep rebound. Perforated patch-clamp recordings reveal that EPG neurons exhibit elevated spontaneous firing following sleep deprivation, which likely depends on an increase in extrinsic excitatory inputs. Our data suggest that cholinergic R5 neurons participate in the homeostatic regulation of sleep, and epistasis experiments indicate that the R5 neurons act upstream of EPG neurons to promote sleep. Finally, we show that the physical and functional connectivity between the R5 and EPG neurons increases with greater sleep need. Importantly, dual patch-clamp recordings demonstrate that activating R5 neurons induces cholinergic-dependent excitatory postsynaptic responses in EPG neurons. Moreover, sleep loss triggers an increase in the amplitude of these responses, as well as in the proportion of EPG neurons that respond. Together, our data support a model whereby sleep drive strengthens the functional connectivity between R5 and EPG neurons, triggering sleep when a sufficient number of EPG neurons are activated. This process could enable the proper timing of the accumulation and release of sleep drive.

0176 Comparing Sleep and Homeostatic Sleep Drive Between Retired Night Shift Workers and Retired Day Workers

Abstract Introduction Retired night shift workers report poorer sleep quality compared to retired day workers, even after returning to a nocturnal sleep schedule, suggesting a potential “scarring” of night shift work on sleep. History of sleep deprivation and sleep at an unfavorable circadian phase may compromise sleep and homeostatic sleep regulation, potentially contributing to poor sleep quality in retired night shift workers. This study compared sleep efficiency and homeostatic sleep regulation in response to sleep deprivation (delta EEG power during NREM sleep, theta EEG power during wakefulness) between retired night shift workers and retired day workers. Methods Participants (N = 75, mean age: 68.3 +/-5.5 years, 51% females, 87% non-Hispanic White) were 35 retired night shift workers and 40 age-, sex-, and race-equated retired day workers. Participants completed a 60-hour laboratory study including one baseline night of sleep, followed by 36 hours of sleep deprivation, followed by one recovery night of sleep. Sleep efficiency and NREM delta EEG power were measured by polysomnography on both nights, and waking theta EEG power was measured every other hour during the 36-hour sleep deprivation period. We analyzed the effects of group (retired night shift workers vs. retired day workers), time (baseline vs. recovery night for sleep efficiency and delta EEG power, hour for theta EEG power), and their interaction on each outcome using linear mixed models. Results Groups did not differ in sleep efficiency averaged across nights (F=1.48, p>0.05) or from baseline to recovery nights (F=0.05, p>0.05). Delta EEG responses to sleep deprivation did not differ by group (F=0.33, p>0.05). Compared to retired day workers, retired night shift workers showed greater overall waking EEG theta power during sleep deprivation (F=13.20, p<0.001). The group by time interaction was not significant (F=0.36, p>0.05), suggesting that group differences in theta EEG power were not due to increased sleep deprivation. Conclusion Sleep efficiency and homeostatic sleep regulation appeared to be preserved in retired night shift workers. Theta EEG power findings suggested greater sleep propensity during wakefulness in retired night shift workers. Interventions to improve sleep quality in retired night shift workers may leverage intact homeostatic sleep regulation mechanisms. Support (If Any) R01AG047139, T32HL082610, T32HL07560, T32MH019986

0250 Greater Slow Wave Activity in Pre-pubertal Children Is Associated With Less Negative Emotional Responses the Following Day

Abstract Introduction Inadequate sleep quantity and/or quality in children is known to forecast development of emotional problems, but how sleep microstructure relates to children’s day-to-day emotional functioning remains unclear. Slow wave activity (SWA), or slow fluctuations of cortical activity during slow wave sleep (SWS) in the frequency range 0.75–4.5 Hz, is a marker of homeostatic sleep regulation and reflects synaptic reorganization of cortical areas early in life (Campbell & Feinberg, 2009). Findings regarding SWA among clinically depressed adolescents are mixed, with evidence of SWA reductions (Lopez et al., 2012) and increases (Tesler et al., 2016) compared to controls. Tesler et al. (2016) also showed SWA in frontal areas correlates positively with depressive thoughts. However, we are unaware of studies examining SWA in relation to depressive symptoms and next-day emotional responses among pre-pubertal children, before developmental declines in SWA (Jenni & Carskadon, 2004). Methods We examined relationships between N3 SWA, depressive symptoms, and next-day emotional responses among N=17 un-medicated, healthy children ages 7-11 years (Tanner 1/2). Children completed a baseline assessment and one night of at-home PSG monitoring (10-hour sleep opportunity) then an in-lab emotional assessment the next day where they provided arousal and valence ratings for negative affective images from the International Affective Picture System. Analyses controlled for PSG night total sleep time, and SWA did not differ by gender. Results Results indicated non-significant associations between SWA and child- and parent-reported depressive symptoms. Greater SWA density across frontal (r=-.66; p< .01), central (r=-.70; p< .001) and occipital regions (r=-.61; p< .01), along with frontal SWA amplitude (r=-.61; p< .01), significantly negatively related to valence ratings for negative images (images were rated as less negative). Conclusion While preliminary, findings suggest potential relationships between SWA and emotional functioning in pre-pubertal children. We have previously shown greater SWS corresponds with less same-week negative affect among pre-pubertal anxious children (Palmer & Alfano, 2017); additionally, in a longitudinal study of pre-pubertal children at risk for depression, greater SWS in childhood protected against later development of depression (Silk et al., 2007). Collectively, findings suggest greater SWA prior to pubertal transition may buffer against negative daytime emotional experiences and later depression. Support (If Any)

Ubiquitin proteasome system in circadian rhythm and sleep homeostasis: Lessons from Drosophila.

Sleep is regulated by two main processes: the circadian clock and sleep homeostasis. Circadian rhythms have been well studied at the molecular level. In the Drosophila circadian clock neurons, the core clock proteins are precisely regulated by post‐translational modifications and degraded via the ubiquitin‐proteasome system (UPS). Sleep homeostasis, however, is less understood; nevertheless, recent reports suggest that proteasome‐mediated degradation of core clock proteins or synaptic proteins contributes to the regulation of sleep amount. Here, we review the molecular mechanism of the UPS and summarize the role of protein degradation in the regulation of circadian clock and homeostatic sleep in Drosophila. Moreover, we discuss the potential interaction between circadian clock and homeostatic sleep regulation with a prime focus on E3 ubiquitin ligases.