Homeostatic Regulation Of Sleep Research Articles

The homeostatic regulation of REM sleep: A role for localized expression of brain-derived neurotrophic factor in the brainstem

Homeostatic regulation of REM sleep plays a key role in neural plasticity and deficits in this process are implicated in the development of many neuropsychiatric disorders. Little is known, however, about the molecular mechanisms that underlie this homeostatic regulation process. This study examined the hypothesis that, during selective REM sleep deprivation (RSD), increased brain-derived neurotrophic factor (BDNF) expression in REM sleep regulating areas is critical for the development of homeostatic drive for REM sleep, as measured by an increase in the number of REM sleep transitions. Rats were assigned to RSD, non-sleep deprived (BSL), or total sleep deprivation (TSD) groups. Physiological recordings were obtained from cortical, hippocampal, and pontine EEG electrodes over a 6h period, in which sleep deprivation occurred during the first 3h. In the RSD, but not the other conditions, homeostatic drive for REM sleep increased progressively. BDNF protein expression was significantly greater in the pedunculopontine tegmentum (PPT) and subcoeruleus nucleus (SubCD) in the RSD as compared to the TSD and BSL groups, areas that regulate REM sleep, but not in the medial preoptic area, which regulates non-REM sleep. There was a significant positive correlation between RSD-induced increases in number of REM sleep episodes and increased BDNF expression in the PPT and SubCD. These increases positively correlated with levels of homeostatic drive for REM sleep. These results, for the first time, suggest that selective RSD-induced increased expression of BDNF in the PPT and SubCD are determinant factors in the development of the homeostatic drive for REM sleep.

Sleep in Populations of Drosophila Melanogaster

The fruit fly Drosophila melanogaster is a diurnal insect active during the day with consolidated sleep at night. Social interactions between pairs of flies have been shown to affect locomotor activity patterns, but effects on locomotion and sleep patterns have not been assessed for larger populations. Here, we use a commercially available locomotor activity monitor (LAM25H) system to record and analyze sleep behavior. Surprisingly, we find that same-sex populations of flies synchronize their sleep/wake activity, resulting in a population sleep pattern, which is similar but not identical to that of isolated individuals. Like individual flies, groups of flies show circadian and homeostatic regulation of sleep, as well as sexual dimorphism in sleep pattern and sensitivity to starvation and a known sleep-disrupting mutation (amnesiac). Populations of flies, however, exhibit distinct sleep characteristics from individuals. Differences in sleep appear to be due to olfaction-dependent social interactions and change with population size and sex ratio. These data support the idea that it is possible to investigate neural mechanisms underlying the effects of population behaviors on sleep by directly looking at a large number of animals in laboratory conditions.

Melatonin Is Required for the Circadian Regulation of Sleep

Sleep is an evolutionarily conserved behavioral state whose regulation is poorly understood. A classical model posits that sleep is regulated by homeostatic and circadian mechanisms. Several factors have been implicated in mediating the homeostatic regulation of sleep, but molecules underlying the circadian mechanism are unknown. Here we use animals lacking melatonin due to mutation of arylalkylamine N-acetyltransferase 2 (aanat2) to show that melatonin is required for circadian regulation of sleep in zebrafish. Sleep is dramatically reduced at night in aanat2 mutants maintained in light/dark conditions, and the circadian regulation of sleep is abolished in free-running conditions. We find that melatonin promotes sleep downstream of the circadian clock as it is not required to initiate or maintain circadian rhythms. Additionally, we provide evidence that melatonin may induce sleep in part by promoting adenosine signaling, thus potentially linking circadian and homeostatic control of sleep.

Glycogen metabolism and the homeostatic regulation of sleep.

In 1995 Benington and Heller formulated an energy hypothesis of sleep centered on a key role of glycogen. It was postulated that a major function of sleep is to replenish glycogen stores in the brain that have been depleted during wakefulness which is associated to an increased energy demand. Astrocytic glycogen depletion participates to an increase of extracellular adenosine release which influences sleep homeostasis. Here, we will review some evidence obtained by studies addressing the question of a key role played by glycogen metabolism in sleep regulation as proposed by this hypothesis or by an alternative hypothesis named “glycogenetic” hypothesis as well as the importance of the confounding effect of glucocorticoïds. Even though actual collected data argue in favor of a role of sleep in brain energy balance-homeostasis, they do not support a critical and direct involvement of glycogen metabolism on sleep regulation. For instance, glycogen levels during the sleep-wake cycle are driven by different physiological signals and therefore appear more as a marker-integrator of brain energy status than a direct regulator of sleep homeostasis. In support of this we provide evidence that blockade of glycogen mobilization does not induce more sleep episodes during the active period while locomotor activity is reduced. These observations do not invalidate the energy hypothesis of sleep but indicate that underlying cellular mechanisms are more complex than postulated by Benington and Heller.

ABSTRACT 66

Background and aims: Critically ill children in the Pediatric Intensive Care Unit (PICU) are exposed to a multitude of risk factors for sleep disturbances, during a time when the restorative benefits of sleep are the most important for neurocognitive development. Increased delta EEG activity during childhood is associated with high levels of synaptic density and activity. Traditional methods of visual inspection of the EEG to determine sleep architecture provide no insight into time-dependent effects of ICU interventions across the sleep period. Aims: Using objective and quantitative data acquisition and analysis techniques, our overall objective is to characterize the sleep experience of critically ill children with EEG and power spectral analysis using the fast Fourier Transform. Methods: After IRB approval and consent, children admitted to the PICU requiring mechanical ventilation for primary respiratory failure had continuous EEG recordings for a minimum of 24 hours. The EEG was analyzed using power spectral analysis with the fast fourier transform (FFT), and the spectral distribution was categorized into frequency bands. ICU subjects were age and gender matched to healthy controls from the TuCASA cohort. Results: Seven critically ill children had EEG recordings for 24 hours or more during mechanical ventilation. When compared to age and gender matched controls, children in the PICU demonstrated no evidence of homeostatic regulation of delta sleep across both the nocturnal and 24 hour periods.FigureConclusions: The results of this study will inform interventional studies to optimize sleep of critically ill children undergoing active neurocognitive development, challenging a PICU paradigm and culture that assumes children are experiencing restorative sleep during critical illness.

Brain‐derived neurotrophic factor gene polymorphism predicts interindividual variation in the sleep electroencephalogram

Previous studies have suggested that brain-derived neurotrophic factor (BDNF) participates in the homeostatic regulation of sleep. The objective of this study was to investigate the influence of the Val66Met functional polymorphism of the BDNF gene on sleep and sleep EEG parameters in a large population-based sample. In total 337 individuals participating in the São Paulo Epidemiologic Sleep Study were selected for analysis. None of the participants had indications of a sleep disorder, as measured by full-night polysomnography and questionnaire. Spectral analysis of the EEG was carried out in all individuals using fast Fourier transformation of the oscillatory signals for each EEG electrode. Sleep and sleep EEG parameters in individuals with the Val/Val genotype were compared with those in Met carriers (Val/Met and Met/Met genotypes). After correction for multiple comparisons and for potential confounding factors, Met carriers showed decreased spectral power in the alpha band in stage one and decreased theta power in stages two and three of nonrapid-eye-movement sleep, at the central recording electrode. No significant influence on sleep macrostructure was observed among the genotype groups. Thus, the Val66Met polymorphism seems to modulate the electrical activity of the brain, predicting interindividual variation of sleep EEG parameters. Further studies of this and other polymorphic variants in potential candidate genes will help the characterization of the molecular basis of sleep.

Identification of Redeye, a new sleep-regulating protein whose expression is modulated by sleep amount

In this study, we report a new protein involved in the homeostatic regulation of sleep in Drosophila. We conducted a forward genetic screen of chemically mutagenized flies to identify short-sleeping mutants and found one, redeye (rye) that shows a severe reduction of sleep length. Cloning of rye reveals that it encodes a nicotinic acetylcholine receptor α subunit required for Drosophila sleep. Levels of RYE oscillate in light-dark cycles and peak at times of daily sleep. Cycling of RYE is independent of a functional circadian clock, but rather depends upon the sleep homeostat, as protein levels are up-regulated in short-sleeping mutants and also in wild type animals following sleep deprivation. We propose that the homeostatic drive to sleep increases levels of RYE, which responds to this drive by promoting sleep. DOI: http://dx.doi.org/10.7554/eLife.01473.001.

Overnight Changes in the Slope of Sleep Slow Waves during Infancy

Slow wave activity (SWA, 0.5-4.5 Hz) is a well-established marker for sleep pressure in adults. Recent studies have shown that increasing sleep pressure is reflected by an increased synchronized firing pattern of cortical neurons, which can be measured by the slope of sleep slow waves. Thus we aimed at investigating whether the slope of sleep slow waves might provide an alternative marker to study the homeostatic regulation of sleep during early human development. All-night sleep electroencephalography (EEG) was recorded longitudinally at 2, 4, 6, and 9 months after birth. Home recording. 11 healthy full-term infants (5 male, 6 female). None. The slope of sleep slow waves increased with age. At all ages the slope decreased from the first to the last hour of non rapid-eye-movement (NREM) sleep, even when controlling for amplitude differences (P < 0.002). The decrease of the slope was also present in the cycle-by-cycle time course across the night (P < 0.001) at the age of 6 months when the alternating pattern of low-delta activity (0.75-1.75 Hz) is most prominent. Moreover, we found distinct topographical differences exhibiting the steepest slope over the occipital cortex. The results suggest an age-dependent increase in synchronization of cortical activity during infancy, which might be due to increasing synaptogenesis. Previous studies have shown that during early postnatal development synaptogenesis is most pronounced over the occipital cortex, which could explain why the steepest slope was found in the occipital derivation. Our results provide evidence that the homeostatic regulation of sleep develops early in human infants.

Diurnal changes in electrocorticogram sleep slow‐wave activity during development in rats

According to the homeostatic regulation of sleep, sleep pressure accumulates during wakefulness, further increases during sleep deprivation and dissipates during subsequent sleep. Sleep pressure is electrophysiologically reflected by electroencephalogram slow-wave activity during non-rapid eye movement sleep, and is thought to be stable across time. During childhood and adolescence the brain undergoes massive reorganization processes. Slow-wave activity during these developmental periods has been shown in humans to follow an inverted U-shaped trajectory, which recently was replicated in rats. The goal of this study was to investigate in rats the diurnal changes of slow-wave activity during the inverted U-shaped developmental trajectory of slow-wave activity. To do so, we performed longitudinal electrocorticogram recordings, and compared the level of slow-wave activity at the beginning with the slow-wave activity level at the end of 24-h baselines in two sets of Sprague-Dawley rats. In younger animals (n=17) we investigated specific postnatal days when overall slow-wave activity increases (postnatal day 26), peaks (postnatal day 28) and decreases (>postnatal day 28). The same analysis was performed in older animals (postnatal day 48, n=6). Our results show a gain of slow-wave activity across 24h on postnatal day 26, followed by no net changes on postnatal day 28, which was then followed by a loss of slow-wave activity during subsequent days (>postnatal day 28). Older animals did not show any net changes in slow-wave activity across 24h. These results cannot be explained by differences in vigilance states. Thus, slow-wave activity during this developmental period may not only reflect the trajectory of sleep pressure but may additionally reflect maturational processes.

Time- and Behavioral State-Dependent Changes in Posterior Hypothalamic GABAA Receptors Contribute to the Regulation of Sleep

Sleep-wake behavior is regulated by a circadian rhythm, homeostatically and by additional mechanisms that determine the timing of slow-wave sleep and rapid eye movement sleep (REMS) episodes. The posterior hypothalamus coordinates the neural and humoral signals with the rest-activity cycle. It contains wake-active neurons, and is a site where stimulation of inhibitory GABAA receptors promotes sleep, whereas their antagonism enhances wakefulness. We explored whether GABAergic mechanisms present in the posterior hypothalamus contribute to the homeostatic and other aspects of sleep-wake regulation. Using micropunches of tissue extracted from either the perifornical (PF) or dorsomedial (DM) regions of the posterior hypothalamus of rats, we determined that mRNA levels for selected subunits of GABAA receptors (β1, β3 and ε) were higher at the end of the active period or following sleep deprivation, when the need for sleep is high, than after several hours of sleep, when sleep need is partially fulfilled. Such a pattern was present in the PF region only, and was consistent with changes in β1 subunit and GABA synthesizing enzyme (GAD) protein levels. In contrast, in the DM region, the levels of GABAA receptor subunit mRNAs and proteins (α1, α2, β1) and GAD varied with circadian time, but were not responsive to sleep deprivation. Separate experiments with sleep-wake monitoring and local perfusion of the PF region with the GABAA receptor antagonist bicuculline revealed that the antagonist had a weaker sleep-reducing effect when sleep need was enhanced by sleep deprivation and that the increased amount of REMS characteristic of the late sleep period was dependent on endogenous GABAergic inhibition. These results support the concept that a varying magnitude of GABAergic inhibition exerted within the PF region contributes to the homeostatic regulation of sleep and shapes its temporal pattern, whereas GABAergic mechanisms in the DM region contribute to circadian regulation.

Sustained Attention Performance during Sleep Deprivation Associates with Instability in Behavior and Physiologic Measures at Baseline

To identify baseline behavioral and physiologic markers that associate with individual differences in sustained attention during sleep deprivation. In a retrospective study, ocular, electrocardiogram, and electroencephalogram (EEG) measures were compared in subjects who were characterized as resilient (n = 15) or vulnerable (n = 15) to the effects of total sleep deprivation on sustained attention. Chronobiology and Sleep Laboratory, Duke-NUS Graduate Medical School Singapore. Healthy volunteers aged 22-32 years from the general population. Subjects were kept awake for at least 26 hours under constant environmental conditions. Every 2 hours, sustained attention was assessed using a 10-minute psychomotor vigilance task (PVT). During baseline sleep and recovery sleep, EEG slow wave activity was similar in resilient versus vulnerable subjects, suggesting that individual differences in vulnerability to sleep loss were not related to differences in homeostatic sleep regulation. Rather, irrespective of time elapsed since wake, subjects who were vulnerable to sleep deprivation exhibited slower and more variable PVT response times, lower and more variable heart rate, and higher and more variable EEG spectral power in the theta frequency band (6.0-7.5 Hz). Performance decrements in sustained attention during sleep deprivation associate with instability in behavioral and physiologic measures at baseline. Small individual differences in sustained attention that are present at baseline are amplified during prolonged wakefulness, thus contributing to large between-subjects differences in performance and sleepiness.

CAV1.2 calcium channel is involved in the circadian regulation of sleep

Two L-type Ca 2+ channels (Cav1.2 & Cav1.3) are expressed in the mouse brain with Cav1.2 contributing to a major proportion (85%). The expression of L-type Ca 2+ channels is greatly densed in the suprachiasmatic nuclei, a neuronal area capable of functioning as autonomous clock and as a generator of circadian rhythms. Although one of the most important aspects regarding the circadian rhythm is the sleep–wake cycle, yet the role of Cav1.2 in the sleep–wake cycle is unclear. Therefore, we investigated whether depletion of Cav1.2 in a transgenic mouse line Cav1.2 (+/−) would alter spontaneous sleep–wake activities. Sleep–wake patterns were monitored by means of EEG and EMG recordings in Cav1.2 (+/−) mice and their wild-type littermates under baseline and sleep deprivation conditions (6 h by gentle handling). Under basal condition, Cav1.2 (+/−) mice showed increased sleep onset latency but subsequent hypersomnolence as compared to wild-type. The hypersomnolence observed in these mice was characterized by higher slow wave activity. Moreover, these heterozygous mice also exhibited drastically shorter wake episodes in the dark period, due to an increased number of NREM sleep episodes. Analysis of sleep architecture further revealed that these mice showed frequent transitions from wake to NREM sleep and vice versa. After sleep deprivation, the sleep onset latency decreased drastically and the trend for higher NREM sleep was observed in Cav1.2 (+/−) mice. Our results demonstrate that depletion of Cav1.2 significantly impacts circadian sleep regulation indicated by increased NREM sleep and decreased time spent in wake in the dark period. However, homeostatic regulation of sleep was unaltered. It has been reported that L-type Ca 2+ channels are involved in wake-promoting effects of hypocretin1. Therefore, decreased wakefulness in Cav1.2 (+/−) mice suggests that a depletion of Cav1.2 might attenuate the hypocretin 1 mediated excitation of wake-related neurons. The alpha-1 subunit of L-type Ca 2+ channels (Cav1.2) is encoded by the CACNA1C gene. Genome-wide association studies (GWAS) have suggested that polymorphisms in the CACNA1C gene are associated with sleep disorders, e.g., insomnia and narcolepsy. Increased sleep onset latency and fragmented sleep architecture displayed by Cav1.2 (+/−) mice might be signs of symptomatic sleep disorders but further studies are needed to elucidate this. Nevertheless, several GWAS studies have significantly associated the CACNA1C gene with psychiatric disorders.

A role for cortical nNOS/NK1 neurons in coupling homeostatic sleep drive to EEG slow wave activity

Although the neural circuitry underlying homeostatic sleep regulation is little understood, cortical neurons immunoreactive for neuronal nitric oxide synthase (nNOS) and the neurokinin-1 receptor (NK1) have been proposed to be involved in this physiological process. By systematically manipulating the durations of sleep deprivation and subsequent recovery sleep, we show that activation of cortical nNOS/NK1 neurons is directly related to non-rapid eye movement (NREM) sleep time, NREM bout duration, and EEG δ power during NREM sleep, an index of preexisting homeostatic sleep drive. Conversely, nNOS knockout mice show reduced NREM sleep time, shorter NREM bouts, and decreased power in the low δ range during NREM sleep, despite constitutively elevated sleep drive. Cortical NK1 neurons are still activated in response to sleep deprivation in these mice but, in the absence of nNOS, they are unable to up-regulate NREM δ power appropriately. These findings support the hypothesis that cortical nNOS/NK1 neurons translate homeostatic sleep drive into up-regulation of NREM δ power through an NO-dependent mechanism.

Acute exposure to evening blue‐enriched light impacts on human sleep

Light in the short wavelength range (blue light: 446-483nm) elicits direct effects on human melatonin secretion, alertness and cognitive performance via non-image-forming photoreceptors. However, the impact of blue-enriched polychromatic light on human sleep architecture and sleep electroencephalographic activity remains fairly unknown. In this study we investigated sleep structure and sleep electroencephalographic characteristics of 30 healthy young participants (16 men, 14 women; age range 20-31years) following 2h of evening light exposure to polychromatic light at 6500K, 2500K and 3000K. Sleep structure across the first three non-rapid eye movement non-rapid eye movement - rapid eye movement sleep cycles did not differ significantly with respect to the light conditions. All-night non-rapid eye movement sleep electroencephalographic power density indicated that exposure to light at 6500K resulted in a tendency for less frontal non-rapid eye movement electroencephalographic power density, compared to light at 2500K and 3000K. The dynamics of non-rapid eye movement electroencephalographic slow wave activity (2.0-4.0Hz), a functional index of homeostatic sleep pressure, were such that slow wave activity was reduced significantly during the first sleep cycle after light at 6500K compared to light at 2500K and 3000K, particularly in the frontal derivation. Our data suggest that exposure to blue-enriched polychromatic light at relatively low room light levels impacts upon homeostatic sleep regulation, as indexed by reduction in frontal slow wave activity during the first non-rapid eye movement episode.

An Epigenetic Model of Insomnia?

Copyright: © 2013 Palagini L, et al. 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. Sleep is a complex physiological process and remain one of the great mysteries of science. Hypotheses for sleep include somatic, metabolic, cellular theories, as well as brain-specific functions such as synaptic plasticity, or synaptic downscaling. Over the past 10 years, genetics provides a new way to address the regulation and function of sleep. Major findings include the identification of loci that make quantitative contributions to sleep characteristics and variability. From Drosophila, zebrafish, and worms to mammalian model organisms, some genes implicated in sleep homeostatic regulation have beeen identified [1]. Circadian genes (Clock, PER1, 2, 3 Bmal1, Timeless), neurotransmitters (serotonin, dopamine, norepinephrine, histamine, acetylcholine, orexin/hypocretin (Orexin/Hcrtrt2), adenosine, GABA receptor), cytokines/immune or stress response genes (NfkB1, NfkB, TNF-α, BiP, IL-1b, IL-6, IL-10), synaptic transmission genes (Homer, c-Fos, Gria3), ion channels (K+ channels, Ca++ channels) and signal metabolic/cellular growth genes (Ghrelin Rho, Leptin EGF, Dwarf, GHRH) have been identified in mammalian. Moreover genetic determinants underlying variability in sleep phenotypes have begun to be revealed and reasearch of the past 10 years focussed on understanding factors contributing to sleep disturbances [2]. Well-documented familial and twin sleep disorder studies suggest an important influence of genetic factors. However only few sleep disorders have an established genetic basis including rare diseases that may result from a single gene mutation: fatal familial insomnia (mutation of prion protein gene PRNP), familial advanced sleep-phase syndrome (mutations in hPER2), delayed sleep phase syndrome (polymorphism in Per3) and narcolepsy with cataplexy (orexin/hypocretin genes) [1,2]. Indeed, most sleep disorders are complex in terms of their genetic susceptibility together with the variable expressivity of the phenotype and contribution of genes. Moreover environment and epigenetic gene-environment interactions have been recently hypothesized to control sleep and its disorders. In Drosophila, several histone modifications have been identified to contribute to chromatin remodeling and thereby to the epigenetic control of circadian gene expression [3]. Recently sleep regulation have been linked to activity-dependent epigenetic brain plasticity [4]. An alteration in both the histone Elp3, essential for the epigenetic control of neurogenesis [5] and the histone Tip60 which epigenetically regulates genes enriched for neuronal functions resulted involved in the sleep-wake regulation encompassing neural network in Drosophila [6]. This latter has been hypothesized to provide insight into epigenetic based regulation of sleep disturbances observed in neurodegenerative diseases like Alzheimer’s disease [6].

Diversity and Noise Effects in a Model of Homeostatic Regulation of the Sleep-Wake Cycle

Recent advances in sleep neurobiology have allowed development of physiologically based mathematical models of sleep regulation that account for the neuronal dynamics responsible for the regulation of sleep-wake cycles and allow detailed examination of the underlying mechanisms. Neuronal systems in general, and those involved in sleep regulation in particular, are noisy and heterogeneous by their nature. It has been shown in various systems that certain levels of noise and diversity can significantly improve signal encoding. However, these phenomena, especially the effects of diversity, are rarely considered in the models of sleep regulation. The present paper is focused on a neuron-based physiologically motivated model of sleep-wake cycles that proposes a novel mechanism of the homeostatic regulation of sleep based on the dynamics of a wake-promoting neuropeptide orexin. Here this model is generalized by the introduction of intrinsic diversity and noise in the orexin-producing neurons, in order to study the effect of their presence on the sleep-wake cycle. A simple quantitative measure of the quality of a sleep-wake cycle is introduced and used to systematically study the generalized model for different levels of noise and diversity. The model is shown to exhibit a clear diversity-induced resonance: that is, the best wake-sleep cycle turns out to correspond to an intermediate level of diversity at the synapses of the orexin-producing neurons. On the other hand, only a mild evidence of stochastic resonance is found, when the level of noise is varied. These results show that disorder, especially in the form of quenched diversity, can be a key-element for an efficient or optimal functioning of the homeostatic regulation of the sleep-wake cycle. Furthermore, this study provides an example of a constructive role of diversity in a neuronal system that can be extended beyond the system studied here.

Challenging the sleep homeostat: Sleep in depression is not premature aging

The close relationship between major depression and sleep disturbances led to the hypothesis of a deficiency in homeostatic sleep pressure in depression (S-deficiency hypothesis). Many observed changes of sleep characteristics in depression are also present in healthy aging, leading to the premise that sleep in depression resembles premature aging. In this study, we aimed at quantifying the homeostatic sleep-wake regulation in young women with major depression and healthy young and older controls under high sleep pressure conditions. After an 8-h baseline night nine depressed women, eight healthy young, and eight healthy older women underwent a 40-h sustained wakefulness protocol followed by a recovery night under constant routine conditions. Polysomnographic recordings were carried out continuously. Sleep parameters as well as the time course of EEG slow-wave activity (SWA) (EEG spectra range: 0.75-4.5 Hz), as a marker of homeostatic sleep pressure, were analyzed during the recovery night. Young depressed women exhibited higher absolute mean SWA levels and a stronger response to sleep deprivation, particularly in frontal brain regions. In contrast, healthy older women exhibited not only attenuated SWA values compared to the other two groups, but also an absence of the frontal SWA predominance. Homeostatic sleep regulation and sleep architecture in young depressed women are not equal to premature aging. Moreover, our findings demonstrate that young moderately depressed women exhibit no deficiency in the sleep homeostatic process S as predicted by the S-deficiency hypothesis, but, rather, live on an elevated level of homeostatic sleep pressure.

軽度断眠は睡眠のホメオスタシス調節を駆動するか

本研究は軽度断眠（部分断眠）が睡眠のホメオスタシス調整を駆動するか否かを実験的に検証した。5名の参加者（19～25歳）は，4夜の自宅睡眠の観測後，睡眠実験室にて連続4夜の睡眠ポリグラフを受けた。就床時刻は第1夜，第2夜および第4夜を午後11時，第3夜を午前2時とした。起床時刻はいずれも午前7時であり，したがって第3夜は総就床時間が5 時間に制限された。レム睡眠関連の睡眠変数の点から実験夜をとおして第1夜効果（ストレス夜）の順応が見られたが，これと対照的に第3夜ではノンレム睡眠と脳波δ帯域パワが睡眠初期の3時間に有意に増えた。第3夜は眠気を除いて出眠後の睡眠感にも改善がみられた。本研究は不眠症改善に適用される睡眠制限療法にホメオスタシス調節が関与する可能性を支持する基本的証拠を提供するものと思われる。

Sleep, Circadian Rhythms, and Interval Timing: Evolutionary Strategies to Time Information

A crucial property of the brain is to integrate temporal information with accurate physiological responses (Hinton and Meck, 1997; Buhusi and Meck, 2005; Coull et al., 2011). Evolution has favored biological clocks that dictate homeostatic processes (e.g., the circadian timing of sleep) and, on a smaller time-scale, timed behavioral responses (e.g., interval timing). The interplay between such time-keeping mechanisms is intriguing but biologically complex. Moreover, in biology, analogous problems can be successfully solved by multiple computations. In this article I will discuss of sleep, circadian rhythms, and interval timing by delineating several aspects that suggest a common evolutionary role in providing neurobiological mechanisms for temporal information processing. Neither interval timing nor the homeostatic regulation of sleep are currently as well-understood, at the molecular level, as the circadian clock. This has triggered a scientific interest in linking these phenomena to the circadian molecular machinery. On one hand, sleep homeostasis has been investigated in genetic and lesion studies of the circadian “master” clock (Franken and Dijk, 2009) to test whether the two processes (homeostatic and circadian) were independent. On the other hand, it has been questioned whether interval timing and circadian clock share similar oscillatory mechanisms, although with a different time-scale (Crystal, 2001, 2006a,b; Crystal and Baramidze, 2007), and whether circadian rhythms affect interval timing. Whilst the research in sleep and circadian clock over the last few years resulted in some interesting positive associations (reviewed in Tucci and Nolan, 2010), the question whether interval timing is related to the circadian clock has not a clear unanimous conclusion yet.

O-13 - Challenging the sleep homeostat in young depressed and healthy older women: sleep in depression is not premature aging

Major depression and sleep disturbances are closely related and often occur concomitantly. Many of the observed changes of sleep characteristics in depression are also present in healthy aging, which led to the premise that sleep in depression resembles premature aging. Here, we aimed at quantifying the homeostatic and circadian sleep-wake regulatory components in young women suffering from major depression disorder and healthy young and older control women during 40 hours of sustained wakefulness. After an 8-h baseline night 9 depressed women, 8 healthy young and 8 healthy older women underwent a 40-hour sustained wakefulness protocol followed by a recovery night under constant routine conditions. Polysomnographic recordings were carried out continuously. Sleep parameters as well as the time course of EEG slow-wave activity (SWA) (EEG spectra range: 0.75-4.5 Hz), as a marker of homeostatic sleep pressure, was analyzed during the recovery night. Young depressed women exhibited higher absolute mean SWA levels and a stronger response to sleep deprivation compared to healthy young and healthy older women, particularly in frontal brain regions. In contrast, healthy older women exhibited attenuated SWA values compared to the other two groups and an absence of the frontal predominance of mean SWA during the recovery night. Our data clearly show that homeostatic sleep regulation as well as sleep architecture in young depressed women is not equal to premature aging. Moreover, our findings demonstrate that young depressed women live on an elevated level of homeostatic sleep pressure.