Molecular Mechanisms of Sleep Homeostasis in Flies and Mammals

Allada, Ravi; Cirelli, Chiara; Sehgal, Amita

doi:10.1101/cshperspect.a027730

Cited by 128 publications

(100 citation statements)

References 207 publications

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“…The R2 network also seems functionally analogous to the thalamus, as network-specific synchronization of slow-wave activity within the thalamus plays a crucial role in maintaining sleep [20][21][22] and sensory gating 35 . Comparable to the potential function of network-specific oscillations during 'local sleep' in vertebrates, slowwave oscillations within the flies' R2 network may well be involved in the homeostatic regulation of synaptic strength 2,7 . We thus suggest that oscillatory network synchronization may represent an evolutionarily selected 'optimal' strategy for sleep regulation as well as for the internal representation of sleepiness.…”

Section: Discussionmentioning

confidence: 99%

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Network-specific synchronization of electrical slow-wave oscillations regulates sleep in Drosophila

Raccuglia

Huang²,

Ender

et al. 2019

Preprint

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Slow-wave rhythms characteristic of deep sleep oscillate in the delta band (0.5 -4 Hz) andcan be found across various brain regions in vertebrates. Across systems it is however unclear how oscillations arise and whether they are the causal functional unit steering behavior. Here, for the first time in any invertebrate, we discover sleep-relevant delta oscillations in Drosophila.We find that slow-wave oscillations in the sleep-regulating R2 network increase with sleep need. Optical multi-unit voltage recordings reveal that single R2 neurons get synchronized by sensory and circadian input pathways. We show that this synchronization depends on NMDA receptor (NMDARs) coincidence detector function and on an interplay of cholinergic and glutamatergic inputs setting a resonance frequency. Genetically targeting the coincidence detector function of NMDARs in R2, and thus the uncovered mechanism underlying synchronization, abolished network-specific slow-wave oscillations. It also disrupted sleep and facilitated light-induced wakening, directly establishing a causal role for slow-wave oscillations in regulating sleep and sensory gating. We therefore propose that the synchronization-based increase in oscillatory power likely represents an evolutionarily conserved, potentially 'optimal', strategy for constructing sleep-regulating sensory gates. that these delta oscillations depend on multi-unit synchronization mediated through NMDA receptor (NMDAR) coincidence detection. Disrupting this synchronization and thus the emergence of compound delta oscillations disrupts sleep and alters sensory gating during sleep. We thus identify slow-wave oscillations as an electrophysiological correlate for sleep regulation in invertebrates and place these oscillatory patterns at the basis of behavior. The sleep-regulating oscillations are comparable to sleep-regulating thalamic oscillations 20-22 as well as network-specific oscillations observed during sleep deprivation in vertebrates (local sleep) 2,23,24 . Our work demonstrates that slow-wave oscillations and sleep are fundamentally interconnected across systems, potentially representing an evolutionarily conserved strategy for network mechanisms regulating internal states and sleep. Results Sleep deprivation increases network-driven delta oscillations in the sleep-regulating R2 networkExamples of rhythmic activity patterns have previously been reported in insects 9,10 .However, their source, function and interdependence with internal states (such as sleep drive), remain largely unclear. We targeted expression of the GEVI ArcLight specifically to R2 neurons in the Drosophila brain. This defined network of 10 cells per hemisphere (Fig. 1a) resides within the ellipsoid body and is involved in sleep regulation [14][15][16] and multi-sensory relay [17][18][19] .In vivo recordings of the dendritic processes (bulb) of R2 neurons (Fig. 1a) identified electrical compound activity (Fig. 1b) that oscillated at delta-band frequencies between 0.5-1.5 Hz (Fig. 1b, d) in rested flies. We sleep-deprived f...

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Section: Discussionmentioning

confidence: 99%

“…Like vertebrates, invertebrates sleep [5][6][7] and behavior selection is sensitive to an animal's sleep need. However, in invertebrates it is unknown whether neural oscillations can gate specific behaviors, and whether an electrophysiological sleep correlate, such as slowwave oscillations, exists or is involved in sleep regulation.…”

Section: Introductionmentioning

confidence: 99%

Network-specific synchronization of electrical slow-wave oscillations regulates sleep in Drosophila

Raccuglia

Huang²,

Ender

et al. 2019

Preprint

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“…In humans, childhood sleep disturbances portend later neurocognitive deficits, possibly because sleep loss impinges on neural circuit formation (Kotagal, 2015;O'Brien, 2009). Although mechanisms controlling mature adult sleep have been uncovered (Allada et al, 2017), the regulation of early life sleep remains poorly understood. 40 Like other animals, the fruit fly, Drosophila melanogaster, exhibits increased sleep duration in young adulthood that tapers with maturity (Dilley et al, 2018;Kayser et al, 2014;Shaw et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Pdm3 directs sleep circuit development to control sleep maturation

Dilley

Szuperák

Williams

et al. 2019

Preprint

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Across species, sleep in young animals is critical for normal brain maturation. In contrast to mature adult sleep, the molecular determinants of early life 20 sleep remain unknown. Through an RNAi-based screen, we identified a gene, pdm3, required for sleep maturation in Drosophila. Pdm3, a transcription factor, acts during nervous system development to coordinate the ingrowth of wake-promoting dopaminergic neurites to a sleep-promoting region. Loss of PDM3 prematurely increases dopaminergic inhibition of the sleep center, abolishing the juvenile sleep 25 state. RNA-Seq/ChIP-Seq and a subsequent modifier screen reveal that pdm3

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“…The sleep state is characterized by extended bouts of behavioral quiescence with a distinct body posture and reduced responsiveness to external stimuli (reviewed in Cirelli and Tononi, 2008; see also Nath et al, 2017;Omond et al, 2017;Raizen et al, 2008;Vorster et al, 2014). Sleep is regulated by the circadian clock, that controls the daily timing of sleep, and by homeostatic mechanisms; extended periods of arousal increase the drive for sleep and can increase subsequent sleep duration or intensity (Allada et al 2017;Blum et al 2018;i.e., slow-wave activity during sleep). The ubiquity of sleep and the evidence for homeostatic need to compensate for lost sleep suggest that it is functionally important.…”

Section: Introductionmentioning

confidence: 99%

Signals from the brood modulate the sleep of brood tending bumblebee workers

Nagari

Jönsson

et al. 2018

Preprint

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Sleep is ubiquitous in vertebrates and invertebrates, and its chronic lost is typically associated with reduced performance, health, or survival. Nevertheless, some animals can give up sleep in order to increase survival or mating opportunities. We studied the interplay between sleep and brood care in the social bumblebee Bombus terrestris. We first used video recording and detailed behavioral analyses to confirm that the bumblebee shows the essential behavioral characteristics of sleep. Based on these analyses we next used immobility bouts of >5' as proxy for sleep in automatic activity monitoring records, and found that sleep is severely reduced in the presence of larvae that require feeding or pupae that are not fed. Reduced sleep was correlated with wax pot building, which is a behavior typical to nest founding mother queens. Sleep was also reduced in the presence of empty cocoons, but this effect was transient and reduced with time. This observation that is consistent with the presence of a sleep modulating pheromonal signal. These results provide the first evidence for brood modulation of sleep in an insect, and are consistent with the hypothesis that plasticity in sleep can evolve as a mechanism to improve care for dependent juveniles.

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Molecular Mechanisms of Sleep Homeostasis in Flies and Mammals

Cited by 128 publications

References 207 publications

Network-specific synchronization of electrical slow-wave oscillations regulates sleep in Drosophila

Network-specific synchronization of electrical slow-wave oscillations regulates sleep in Drosophila

Pdm3 directs sleep circuit development to control sleep maturation

Signals from the brood modulate the sleep of brood tending bumblebee workers

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