Energy Scarcity Promotes a Brain-wide Sleep State Modulated by Insulin Signaling in C. elegans

Abstract

SummaryNeural information processing entails a high energetic cost, but its maintenance is crucial for animal survival. However, the brain’s energy conservation strategies are incompletely understood. Employing functional brain-wide imaging and quantitative behavioral assays, we describe a neuronal strategy in Caenorhabditis elegans that balances energy availability and expenditure. Upon acute food deprivation, animals exhibit a transiently elevated state of arousal, indicated by foraging behaviors and increased responsiveness to food-related cues. In contrast, long-term starvation suppresses these behaviors and biases animals to intermittent sleep episodes. Brain-wide neuronal population dynamics, which are likely energetically costly but important for behavior, are robust to starvation while animals are awake. However, during starvation-induced sleep, brain dynamics are systemically downregulated. Neuromodulation via insulin-like signaling is required to transiently maintain the animals’ arousal state upon acute food deprivation. Our data suggest that the regulation of sleep and wakefulness supports optimal energy allocation.

Automated analysis of sleep in adultC. eleganswith closed-loop assessment of state-dependent neural activity

“…Notably, hypoxia increased sleep fraction only after 4 h in the device (P<0.0001, Fig. 2c), in line with past results suggesting that starvation and hypoxia work together to promote sleep behavior 31 . The rapid rise in sleep behavior after 4 h mimicked a similar rise in static no-flow conditions ( Fig.…”

“…1h). Under static conditions, animals can deplete the microfluidic environment of oxygen 57,58 , and hypoxia has been shown to induce sleep behavior 59 especially in starved animals 31 .…”

“…Because feeding state impacts arousal 61,62 and starvation may regulate the impact of hypoxia on sleep 31 , we next assessed the role of feeding and satiety on adult sleep dynamics within our microfluidic chamber ( Fig. 2d-f).…”

“…C. elegans demonstrate states of quiescence during lethargus between larval stages 26 (developmental sleep) and during periods of stress 27 , satiety 28,29 , starvation 30,31 , and hypoxia 32 . Additionally, adult C. elegans undergo quiescent periods after 1-2 h of swimming in liquid 33 and in microfluidic chambers with open and constrictive geometries 34 .…”

“…Neural activity measurements typically require immobilization by agarose pads 50 or microfluidic traps 38 , which prevent locomotory behavior and limit their use to developmentally-timed sleep in which sleep state is inferred by timing rather than by behavior. Alternatively, whole brain imaging in immobilized adult animals 31,32 showed cessation of spontaneous neural activity during presumed sleep states induced by hypoxia. However, spontaneous sleep events in adult animals are best assessed by analysis of locomotion and quiescent behaviors.…”