Is Sleep Essential?

No current hypothesis can explain why animals need to sleep. Yet, sleep is universal, tightly regulated, and cannot be deprived without deleterious consequences. This suggests that searching for a core function of sleep, particularly at the cellular level, is still a worthwhile exercise

Time to Be SHY? Some Comments on Sleep and Synaptic Homeostasis

Sleep must serve an essential, universal function, one that offsets the risk of being disconnected from the environment. The synaptic homeostasis hypothesis (SHY) is an attempt to identify this essential function. Its core claim is that sleep is needed to reestablish synaptic homeostasis, which is challenged by the remarkable plasticity of the brain. In other words, sleep is “the price we pay for plasticity.” In this issue, M. G. Frank reviewed several aspects of the hypothesis and raised several issues. The comments below provide a brief summary of the motivations underlying SHY and clarify that SHY is a hypothesis not about specific mechanisms, but about a universal, essential function of sleep. This function is the preservation of synaptic homeostasis in the face of a systematic bias toward a net increase in synaptic strength—a challenge that is posed by learning during adult wake, and by massive synaptogenesis during development

Sleep, aging, and lifespan in Drosophila

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies in humans suggest that a decrease in daily sleep duration is associated with reduced lifespan, but this issue remains controversial. Other studies in humans also show that both sleep quantity and sleep quality decrease with age. <it>Drosophila melanogaster </it>is a useful model to study aging and sleep, and inheriting mutations affecting the potassium current Shaker results in flies that sleep less and have a shorter lifespan. However, whether the link between short sleep and reduced longevity exists also in wild-type flies is unknown. Similarly, it is unknown whether such a link depends on sleep amount per se, rather than on other factors such as waking activity. Also, sleep quality has been shown to decrease in old flies, but it remains unclear whether aging-related sleep fragmentation is a generalized phenomenon.</p> <p>Results</p> <p>We compared 3 short sleeping mutant lines (<it>Hk</it>¹, <it>Hk</it>^{<it>Y </it>}and <it>Hk</it>²) carrying a mutation in Hyperkinetic, which codes for the beta subunit of the Shaker channel, to wild-type siblings throughout their entire lifespan (all flies kept at 20°C). <it>Hk</it>¹and <it>Hk</it>^{<it>Y </it>}mutants were short sleeping relative to wild-type controls from day 3 after eclosure, and <it>Hk</it>²flies became short sleepers about two weeks later. All 3 <it>Hk </it>mutant lines had reduced lifespan relative to wild-type flies. Total sleep time showed a trend to increase in all lines with age, but the effect was most pronounced in <it>Hk</it>¹and <it>Hk</it>^{<it>Y </it>}flies. In both mutant and wild-type lines sleep quality did not decay with age, but the strong preference for sleep at night declined starting in "middle age". Using Cox regression analysis we found that in <it>Hk</it>¹and <it>Hk</it>^{<it>Y </it>}mutants and their control lines there was a negative relationship between total sleep amount during the first 2 and 4 weeks of age and hazard (individual risk of death), while no association was found in <it>Hk</it>²flies and their wild-type controls. <it>Hk</it>¹and <it>Hk</it>^{<it>Y </it>}mutants and their control lines also showed an association between total daily wake activity over the first 2 and 4 weeks of age and hazard. However, when both sleep duration and wake activity were used in the same regression, the effects of activity were much reduced, while most of the sleep effects remained significant. Finally, <it>Hk</it>¹flies and wild-type siblings were also tested at 25°C, and results were similar to those at 20°C. Namely, <it>Hk</it>¹mutants were short sleeping, hyperactive, and short lived relative to controls, and sleep quality in both groups did not decrease with age.</p> <p>Conclusions</p> <p>Different <it>Hk </it>mutations affect the sleep phenotype, and do so in an age-dependent manner. In 4 of the 6 lines tested sleep associates significantly with lifespan variation even after any effect of activity is removed, but activity does not associate significantly with lifespan after the effects of sleep are removed. Thus, in addition to environmental factors and genetic background, sleep may also affect longevity. Sleep quality does not necessarily decay as flies age, suggesting that aging-related sleep fragmentation may also depend on many factors, including genetic background and rearing conditions.</p

Only what exists can cause: An intrinsic view of free will

This essay addresses the implications of integrated information theory (IIT) for free will. IIT is a theory of what consciousness is and what it takes to have it. According to IIT, the presence of consciousness is accounted for by a maximum of cause-effect power in the brain. Moreover, the way specific experiences feel is accounted for by how that cause-effect power is structured. If IIT is right, we do have free will in the fundamental sense: we have true alternatives, we make true decisions, and we - not our neurons or atoms - are the true cause of our willed actions and bear true responsibility for them. IIT's argument for true free will hinges on the proper understanding of consciousness as true existence, as captured by its intrinsic powers ontology: what truly exists, in physical terms, are intrinsic entities, and only what truly exists can cause.Comment: 26 pages, 12 figure

Homeostatic regulation of sleep in the white-crowned sparrow (Zonotrichia leucophrys gambelii)

<p>Abstract</p> <p>Background</p> <p>Sleep is regulated by both a circadian and a homeostatic process. The homeostatic process reflects the duration of prior wakefulness: the longer one stays awake, the longer and/or more intense is subsequent sleep. In mammals, the best marker of the homeostatic sleep drive is slow wave activity (SWA), the electroencephalographic (EEG) power spectrum in the 0.5–4 Hz frequency range during non-rapid eye movement (NREM) sleep. In mammals, NREM sleep SWA is high at sleep onset, when sleep pressure is high, and decreases progressively to reach low levels in late sleep. Moreover, SWA increases further with sleep deprivation, when sleep also becomes less fragmented (the duration of sleep episodes increases, and the number of brief awakenings decreases). Although avian and mammalian sleep share several features, the evidence of a clear homeostatic response to sleep loss has been conflicting in the few avian species studied so far. The aim of the current study was therefore to ascertain whether established markers of sleep homeostasis in mammals are also present in the white-crowned sparrow (<it>Zonotrichia leucophrys gambelii</it>), a migratory songbird of the order Passeriformes. To accomplish this goal, we investigated amount of sleep, sleep time course, and measures of sleep intensity in 6 birds during baseline sleep and during recovery sleep following 6 hours of sleep deprivation.</p> <p>Results</p> <p>Continuous (24 hours) EEG and video recordings were used to measure baseline sleep and recovery sleep following short-term sleep deprivation. Sleep stages were scored visually based on 4-sec epochs. EEG power spectra (0.5–25 Hz) were calculated on consecutive 4-sec epochs. Four vigilance states were reliably distinguished based on behavior, visual inspection of the EEG, and spectral EEG analysis: Wakefulness (W), Drowsiness (D), slow wave sleep (SWS) and rapid-eye movement (REM) sleep. During baseline, SWA during D, SWS, and NREM sleep (defined as D and SWS combined) was highest at the beginning of the major sleep period and declined thereafter. Moreover, peak SWA in both SWS and NREM sleep increased significantly immediately following sleep deprivation relative to baseline.</p> <p>Conclusion</p> <p>As in mammals, sleep deprivation in the white-crowned sparrow increases the intensity of sleep as measured by SWA.</p

Sleep in Kcna2 knockout mice

<p>Abstract</p> <p>Background</p> <p><it>Shaker </it>codes for a <it>Drosophila </it>voltage-dependent potassium channel. Flies carrying <it>Shaker </it>null or hypomorphic mutations sleep 3–4 h/day instead of 8–14 h/day as their wild-type siblings do. Shaker-like channels are conserved across species but it is unknown whether they affect sleep in mammals. To address this issue, we studied sleep in <it>Kcna2 </it>knockout (KO) mice. <it>Kcna2 </it>codes for Kv1.2, the alpha subunit of a Shaker-like voltage-dependent potassium channel with high expression in the mammalian thalamocortical system.</p> <p>Results</p> <p>Continuous (24 h) electroencephalograph (EEG), electromyogram (EMG), and video recordings were used to measure sleep and waking in <it>Kcna2 </it>KO, heterozygous (HZ) and wild-type (WT) pups (P17) and HZ and WT adult mice (P67). Sleep stages were scored visually based on 4-s epochs. EEG power spectra (0–20 Hz) were calculated on consecutive 4-s epochs. KO pups die by P28 due to generalized seizures. At P17 seizures are either absent or very rare in KO pups (< 1% of the 24-h recording time), and abnormal EEG activity is only present during the seizure. KO pups have significantly less non-rapid eye movement (NREM) sleep (-23%) and significantly more waking (+21%) than HZ and WT siblings with no change in rapid eye movement (REM) sleep time. The decrease in NREM sleep is due to an increase in the number of waking episodes, with no change in number or duration of sleep episodes. Sleep patterns, daily amounts of sleep and waking, and the response to 6 h sleep deprivation are similar in HZ and WT adult mice.</p> <p>Conclusion</p> <p>Kv1.2, a mammalian homologue of Shaker, regulates neuronal excitability and affects NREM sleep.</p

Sleep Loss Promotes Astrocytic Phagocytosis and Microglial Activation in Mouse Cerebral Cortex

We previously found that Mertk and its ligand Gas6, astrocytic genes involved in phagocytosis, are upregulated after acute sleep deprivation. These results suggested that astrocytes may engage in phagocytic activity during extended wake, but direct evidence was lacking. Studies in humans and rodents also found that sleep loss increases peripheral markers of inflammation, but whether these changes are associated with neuroinflammation and/or activation of microglia, the brain's resident innate immune cells, was unknown. Here we used serial block-face scanning electron microscopy to obtain 3D volume measurements of synapses and surrounding astrocytic processes in mouse frontal cortex after 6-8 h of sleep, spontaneous wake, or sleep deprivation (SD) and after chronic (∼5 d) sleep restriction (CSR). Astrocytic phagocytosis, mainly of presynaptic components of large synapses, increased after both acute and chronic sleep loss relative to sleep and wake. MERTK expression and lipid peroxidation in synaptoneurosomes also increased to a similar extent after short and long sleep loss, suggesting that astrocytic phagocytosis may represent the brain's response to the increase in synaptic activity associated with prolonged wake, clearing worn components of heavily used synapses. Using confocal microscopy, we then found that CSR but not SD mice show morphological signs of microglial activation and enhanced microglial phagocytosis of synaptic elements, without obvious signs of neuroinflammation in the CSF. Because low-level sustained microglia activation can lead to abnormal responses to a secondary insult, these results suggest that chronic sleep loss, through microglia priming, may predispose the brain to further damage.SIGNIFICANCE STATEMENT We find that astrocytic phagocytosis of synaptic elements, mostly of presynaptic origin and in large synapses, is upregulated already after a few hours of sleep deprivation and shows a further significant increase after prolonged and severe sleep loss, suggesting that it may promote the housekeeping of heavily used and strong synapses in response to the increased neuronal activity of extended wake. By contrast, chronic sleep restriction but not acute sleep loss activates microglia, promotes their phagocytic activity, and does so in the absence of overt signs of neuroinflammation, suggesting that like many other stressors, extended sleep disruption may lead to a state of sustained microglia activation, perhaps increasing the brain's susceptibility to other forms of damage