Most sleep does not serve a vital function. Evidence from <i>Drosophila melanogaster</i>

Geissmann, Quentin; Beckwith, Esteban J.; Gilestro, Giorgio F.

doi:10.1101/361667

Cited by 16 publications

(25 citation statements)

References 52 publications

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“…Consistent with P(Wake) driving the expression of rebound sleep, the total amount of rebound is more strongly correlated with change in P(Wake) (R = −0.97, P < 0.0001) than change in P(Doze) (R = 0.19, P = 0.06), and the effect size of the change in P(Wake) is larger than the effect size of P(Doze) (Cohen's d = −1.46 and 0.81, respectively) (32). One implication of this result is that the magnitude of rebound sleep is a flawed measure of sleep homeostasis, consistent with recent reports (21). Interestingly, P(Doze) also appears to be regulated by "wake pressure" in addition to sleep pressure.…”

Section: Resultssupporting

confidence: 86%

“…S2). Previous research has found that each fly has an idiosyncratic preference for a range of behaviors, including total daily sleep (20,21). We find that P(Wake) and P(Doze) are similarly idiosyncratic, but the population mean is a reasonable estimate of the central tendency of the P(Wake) and P(Doze) distributions for WT flies (SI Appendix, Fig.…”

Section: Resultsmentioning

confidence: 53%

“…Alternatively, it may be that the two-process model simply does not reflect regulation of sleep pressure in Drosophila. Recent evidence suggests that sleep pressure in flies is primarily regulated by the circadian clock rather than by sleep debt (21). The lack of agreement between model and empirical results suggests the need for a revised and more broadly based model of sleep drives.…”

Section: Discusssionmentioning

confidence: 99%

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Covert sleep-related biological processes are revealed by probabilistic analysis in Drosophila

Wiggin

Goodwin

Donelson

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Sleep pressure and sleep depth are key regulators of wake and sleep. Current methods of measuring these parameters in Drosophila melanogaster have low temporal resolution and/or require disrupting sleep. Here we report analysis tools for high-resolution, noninvasive measurement of sleep pressure and depth from movement data. Probability of initiating activity, P(Wake), measures sleep depth while probability of ceasing activity, P(Doze), measures sleep pressure. In vivo and computational analyses show that P(Wake) and P(Doze) are largely independent and control the amount of total sleep. We also develop a Hidden Markov Model that allows visualization of distinct sleep/wake substates. These hidden states have a predictable relationship with P(Doze) and P(Wake), suggesting that the methods capture the same behaviors. Importantly, we demonstrate that both the Doze/Wake probabilities and the sleep/wake substates are tied to specific biological processes. These metrics provide greater mechanistic insight into behavior than measuring the amount of sleep alone.

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Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 53%

Section: Discusssionmentioning

confidence: 99%

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Covert sleep-related biological processes are revealed by probabilistic analysis in Drosophila

Wiggin

Goodwin

Donelson

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Alternatively, it may be that the two-process model simply does not reflect regulation of sleep pressure in Drosophila . Recent evidence suggests that sleep pressure in flies is primarily regulated by the clock rather than by sleep debt (Geissmann et al 2019). The lack of agreement between model and empirical results suggests the need for a revised and more broadly-based model of sleep drives.…”

Section: Discusssionmentioning

confidence: 99%

State-Switching Probability Reveals Sleep-Related Biological Drives inDrosophila

Wiggin

Goodwin

Donelson

et al. 2018

Preprint

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Acknowledgements 25We would like to thank Dr. Jané Kondev and the students in the Brandeis Quantitative 26Biology Research Community (QBReC) who assisted in collecting preliminary data. 28 Grants 30This work was funded by R01 MH067284 (to LCG) and F32 NS098624 (to TDW). 32. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/263301 doi: bioRxiv preprint first posted online Feb. 12, 2018; 2 ABSTRACT 33In humans and flies, sleep is a highly organized behavior, occurring in discrete bouts 34 that are consolidated at night but have a more fragmented structure during the day.

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“…Animals with much smaller nervous systems, such as insects, also sleep (1)(2)(3)(4)(5)(6)(7)(8). Mechanisms that control sleep include circadian circuits, which underlie daily rhythms of sleep and other biological variables (9).…”

mentioning

confidence: 99%

On the cause of sleep: Protein fragments, the concept of sentinels, and links to epilepsy

Varshavsky

2019

Proc. Natl. Acad. Sci. U.S.A.

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The molecular-level cause of sleep is unknown. In 2012, we suggested that the cause of sleep stems from cumulative effects of numerous intracellular and extracellular protein fragments. According to the fragment generation (FG) hypothesis, protein fragments (which are continually produced through nonprocessive cleavages by intracellular, intramembrane, and extracellular proteases) can be beneficial but toxic as well, and some fragments are eliminated slowly during wakefulness. We consider the FG hypothesis and propose that, during wakefulness, the degradation of accumulating fragments is delayed within natural protein aggregates such as postsynaptic densities (PSDs) in excitatory synapses and in other dense protein meshworks, owing to an impeded diffusion of the ∼3,000-kDa 26S proteasome. We also propose that a major function of sleep involves a partial and reversible expansion of PSDs, allowing an accelerated destruction of PSD-localized fragments by the ubiquitin/proteasome system. Expansion of PSDs would alter electrochemistry of synapses, thereby contributing to a decreased neuronal firing during sleep. If so, the loss of consciousness, a feature of sleep, would be the consequence of molecular processes (expansions of protein meshworks) that are required for degradation of protein fragments. We consider the concept of FG sentinels, which signal to sleep-regulating circuits that the levels of fragments are going up. Also discussed is the possibility that protein fragments, which are known to be overproduced during an epileptic seizure, may contribute to postictal sleep and termination of seizures. These and related suggestions, described in the paper, are compatible with current evidence about sleep and lead to testable predictions. fragment | extracellular | intracellular | proteolysis | sleep S leep is universal among mammals and other vertebrates.Animals with much smaller nervous systems, such as insects, also sleep (1-8). Mechanisms that control sleep include circadian circuits, which underlie daily rhythms of sleep and other biological variables (9). However, circadian aspects of sleep do not define it entirely, because sleep has the homeostatic property of becoming longer after sleep deprivation (10, 11). In mammals, birds, and lizards, two alternating modes of sleep have been identified, the non-rapid eye movement (NREM) sleep and the rapid eye movement (REM) sleep (12,13). The depth of NREM sleep is yet another sleep variable. In adult humans, NREM sleep occupies ∼80% of the total sleep time. For recent reviews of sleep, see refs. 14-20.Despite advances in the understanding of neuronal circuits as well as genes, proteins, short peptides, and other compounds that regulate sleep, it is largely unknown why sleep exists and what it is for. Maladaptive aspects of sleep include elevated dangers of predation during sleep, the neglect of territorial defense and foraging for food, and the loss of parental care and mating opportunities. It is unknown what features of sleep did not allow these fitness costs to ca...

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Most sleep does not serve a vital function. Evidence from Drosophila melanogaster

Cited by 16 publications

References 52 publications

Covert sleep-related biological processes are revealed by probabilistic analysis in Drosophila

Covert sleep-related biological processes are revealed by probabilistic analysis in Drosophila

State-Switching Probability Reveals Sleep-Related Biological Drives inDrosophila

On the cause of sleep: Protein fragments, the concept of sentinels, and links to epilepsy

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