Coherent multi-level network oscillations create neural filters to favor quiescence over navigation in Drosophila

Abstract

Quiescent states such as sleep restore vital physiological functions across phyla and are characterized by reduced locomotion and diminished behavioral responsiveness to external stimuli. In humans, synchronous activity across cortical networks is a hallmark of deep sleep, but how network coherence elevates arousal thresholds to maintain quiescent states remains largely unclear. Here, we build on our recent discovery of slow wave activity (SWA) mediating sleep need in the R5 ring network of Drosophila and investigate interactions across sleep- and arousal mediating networks. We demonstrate that information of sleep need travels across a recently described recurrent network for sleep regulation (dFSB-helicon-R5) and elicits oscillatory Ca2+ signatures in the presynaptic terminals of the interconnected networks. Subject to circadian modulation, the sleep need mediating circuits within this network (dFSB and R5) reciprocally promote these oscillatory signatures. Optogenetically imposing slow rhythms (1 Hz) on R5 and dFSB induces entrainable quiescent states while high-frequency stimulation of R5 (10 Hz) leads to flies losing postural control. We further discover that increased excitability in the master sleep homeostat (dFSB) likely acts as a switch that synchronizes the presynaptic electrical patterns of R5 and arousal mediating neurons (helicon) at night. Exposing the behavioral significance by optogenetically mimicking coherent activity we show that R5/helicon synchronization facilitates suppression of responsiveness to visual stimuli in sleeping flies. Moreover, neural activity in downstream head-direction neurons targeted by both helicon and R5 can be completely inhibited through activation of the R5 network. We therefore propose that sleep need mediating circuits promote coherent SWA to induce quiescent states by rhythmically associating neural networks that mediate locomotion, arousal and postural control.

A half-centre oscillator encodes sleep pressure

“…Our work, along with previous studies [27][28][29][30] , has uncovered remarkable parallels and striking differences in the sleep-related neuronal dynamics of flies and mammals. Slow waves reflecting alternating UP and DOWN states are a common marker of sleep pressure, but the biophysical origin, spatial spread, and temporal persistence of these waves differ.…”

“…Previous reports of sleep-related rhythms 27,28 , and in particular observations of SWA in parts of the central complex 29,30 (R5 neurons and dFBNs), noted but could not explore possible parallels with NREM sleep because the studies were performed ex vivo and without a simultaneous behavioral read-out of vigilance state. It is thus unclear if the occurrence of dFBN delta oscillations defines a slow-wave sleep stage as in mammals or if SWA tracks variations in sleep pressure throughout the sleep-wake cycle.…”

A neuronal substrate for translating nutrient state and resource density estimations into foraging decisions

“…Most prominent is the role of dFB neurons in modulating sleep upon sleep deprivation and changes in diet (Donlea et al, 2014(Donlea et al, , 2018French et al, 2021). These studies and our work suggest that dFB neurons receive internal state information (be it about the sleep state or the nutritional state of the animal) to gate how sensory information is used to shape motor outputs (Donlea et al, 2014(Donlea et al, , 2018Carvalho-Santos and Ribeiro, 2023;Raccuglia et al, 2022). Therefore, we propose that FB6 neurons receive information about the internal protein state of the animal as well as the density of food in the environment, and modulate the animal's decision on whether or not to engage with a food patch.…”

Multivariate classification of multichannel long-term electrophysiology data identifies different sleep stages in fruit flies

“…Our multichannel recording preparation therefore approximates as closely as possible—in flies—a sleep EEG, which has been the starting point for most discussions on sleep physiology in other animals. The human sleep EEG has defined the sleep stages that are now being investigated in other animals ( 46 , 50 – 52 ), although this is obviously a neocortical view with potentially little relevance to animals lacking the neural architecture giving rise to sleep signatures such as delta (1 to 4 Hz) during slow-wave sleep or theta (5 to 8 Hz) during REM sleep ( 53 ).…”