Highlights d Rhythmic mechanosensory stimulation (aka rocking) promotes sleep also in the mouse d Linear acceleration applied to the head encodes the rocking stimulus d The rocking effects on sleep are acceleration and time specific d The otolithic organs of the vestibular system mediate the rocking effects on sleep

Sleep-wake driven changes in non-rapid-eye-movement sleep (NREM) sleep (NREMS) EEG delta (δ-)power are widely used as proxy for a sleep homeostatic process. Here, we noted frequency increases in δ-waves in sleep-deprived mice, prompting us to re-evaluate how slow-wave characteristics relate to prior sleep-wake history. We identified two classes of δ-waves; one responding to sleep deprivation with high initial power and fast, discontinuous decay during recovery sleep (δ2) and another unrelated to time-spent-awake with slow, linear decay (δ1). Reanalysis of previously published datasets demonstrates that δ-band heterogeneity after sleep deprivation is also present in human subjects. Similar to sleep deprivation, silencing of centromedial thalamus neurons boosted subsequent δ2-waves, specifically. δ2-dynamics paralleled that of temperature, muscle tone, heart rate, and neuronal ON-/OFF-state lengths, all reverting to characteristic NREMS levels within the first recovery hour. Thus, prolonged waking seems to necessitate a physiological recalibration before typical NREMS can be reinstated.

The timing and duration of sleep results from the interaction between a homeostatic sleep-wake-driven process and a periodic circadian process, and involves changes in gene regulation and expression. Unraveling the contributions of both processes and their interaction to transcriptional and epigenomic regulatory dynamics requires sampling over time under conditions of unperturbed and perturbed sleep. We profiled mRNA expression and chromatin accessibility in the cerebral cortex of mice over a 3-d period, including a 6-h sleep deprivation (SD) on day 2. We used mathematical modeling to integrate time series of mRNA expression data with sleep-wake history, which established that a large proportion of rhythmic genes are governed by the homeostatic process with varying degrees of interaction with the circadian process, sometimes working in opposition. Remarkably, SD caused long-term effects on gene-expression dynamics, outlasting phenotypic recovery, most strikingly illustrated by a damped oscillation of most core clock genes, including Arntl/Bmal1, suggesting that enforced wakefulness directly impacts the molecular clock machinery. Chromatin accessibility proved highly plastic and dynamically affected by SD. Dynamics in distal regions, rather than promoters, correlated with mRNA expression, implying that changes in expression result from constitutively accessible promoters under the influence of enhancers or repressors. Serum response factor (SRF) was predicted as a transcriptional regulator driving immediate response, suggesting that SRF activity mirrors the build-up and release of sleep pressure. Our results demonstrate that a single, short SD has long-term aftereffects at the genomic regulatory level and highlights the importance of the sleep-wake distribution to diurnal rhythmicity and circadian processes. circadian | sleep | gene expression | epigenetics | long-term effects A ccording to the 2-process model (1, 2), sleep regulation results from an interaction between a sleep homeostatic process and a circadian process often referred to as "process S" and "process C," respectively. The sleep homeostat tracks the need or pressure for sleep as it increases during wake and decreases during sleep, while the circadian process dictates the optimal time of day for sleep to occur. Their fine-tuned interaction assures optimal timing, duration, and quality of both wakefulness and sleep, and even minor changes in either of these processes or their alignment cause performance decrements and clinically significant sleep disruption (3,4).The circadian clock is described as self-sustained ∼24-h oscillations involved in a variety of physiological processes and behaviors, such as sleep (3,5). It is encoded molecularly through negative feedback loops involving the core clock genes, which are capable of generating oscillations in constant environmental conditions; that is, in the absence of periodically occurring time cues such as the light/dark cycle (6). However, this apparent autonomy does not inevitably imply that the expressi...

SUMMARYA few investigations have raised the question of a possible relationship between obstructive sleep apnoea syndrome (OSAS) and floppy eyelid syndrome (FES). FES is an easily inverted floppy eyelid with papillary conjunctivis, and is a subset of the general pathology, lax eyelid syndrome. The aim of the current study is to determine whether OSAS severity is associated with FES. One hundred and 27 consecutive subjects (aged 25-75 years) referred to the Strasbourg University Sleep Clinic with suspicion of OSAS were included. All patients underwent overnight ambulatory respiratory polygraphy, comprehensive ophthalmological examination and completed standard sleep questionnaires. OSAS severity was defined based on the patientÕs obstructive apnoeahypopnoea index (AHI). As expected, age, body mass index (BMI) and the proportion of males increased with OSAS severity. FES was observed in 15.8% of the subjects without OSAS, 25.8% of the total OSAS population and the frequency was significantly increased (40%) in patients with severe OSAS (AHI > 30 h )1 ). A significant correlation between OSAS severity and FES was found after adjustment for age, sex and BMI, using a principal component analysis (PCA). The multivariate analysis included clinical, polygraphic and comorbidity data and was followed by logistic regressions for the main components extracted from the PCA. In summary, our findings show an association between OSAS severity and FES and suggest that severe OSAS might be an independent risk factor for FES. These two disorders may share common biological determinants, such as tissue elasticity. Finally, clinicians should be aware of this association so that underlying OSAS or FES can be detected. IN TROD UCTI ONRecent investigations have suggested a relationship between obstructive sleep apnoea syndrome (OSAS) and different ophthalmological disorders, such as chronic open angle glaucoma, non-arteritic anterior ischaemic optic neuropathy, keratoconus and floppy eyelid syndrome (FES) (Abdal et al.,

No abstract

Sleep depriving mice affects clock-gene expression, suggesting that these genes contribute to sleep homeostasis. The mechanisms linking extended wakefulness to clock-gene expression are, however, not well understood. We propose CIRBP to play a role because its rhythmic expression is i) sleep-wake driven and ii) necessary for high-amplitude clock-gene expression in vitro. We therefore expect Cirbp knock-out (KO) mice to exhibit attenuated sleep-deprivation-induced changes in clock-gene expression, and consequently to differ in their sleep homeostatic regulation. Lack of CIRBP indeed blunted the sleep-deprivation incurred changes in cortical expression of Nr1d1, whereas it amplified the changes in Per2 and Clock. Concerning sleep homeostasis, KO mice accrued only half the extra REM sleep wild-type (WT) littermates obtained during recovery. Unexpectedly, KO mice were more active during lights-off which was accompanied with faster theta oscillations compared to WT mice. Thus, CIRBP adjusts cortical clock-gene expression after sleep deprivation and expedites REM-sleep recovery.

No abstract

Sleep deprivation, in the context of shift work, is an increasing major public health issue. We aimed to determine whether early light administration can counteract sleep deprivation effects, and to compare LED-glasses with a traditional light therapy box. This cross-over design study included 18 individuals exposed to light therapy for 30 minutes at 5 am after one night of complete sleep deprivation, to mimic the night shift condition. Individuals were randomly exposed to 10,000 Lux light box, 2,000 Lux LED blue-enriched glasses, and control (ambient dim-light at 8 lux). Alertness, cognition and mood were assessed throughout the night and following morning. Five women and 13 men (mean 24.78 year old) presented with a progressive and increasing alteration of alertness, cognition, and mood during each sleep deprivation. A rebound was observed at 8 am resulting from the circadian drive overriding cumulative sleep homeostatic effects. Morning light significantly improved sleepiness and sustained attention from 5 to 7 am. These effects were comparable between devices and significantly different from control. Both devices were overall well and similarly tolerated. Early morning light therapy in the condition of sleep loss may have broad practical applications to improve sleepiness, sustained attention and subsequent risk of accidents.