Satiety, Thermosensation and Mechanosensation Regulate a Spontaneous C. elegans Sleep State

Abstract

One remarkable feature of the nervous system is its ability to rapidly and spontaneously switch between activity states. In the extreme example of sleep, animals arrest locomotion, reduce their sensitivity to sensory stimuli, and dramatically alter their neural activity. Small organisms are useful models to better understand these sudden changes in neural states because we can simultaneously observe whole-brain activity, monitor behavior and precisely regulate the external environment. Here, we show a spontaneous sleep-like behavior in C. elegans that is associated with a distinct global-brain state and regulated by both the animals internal physiological state and input from multiple sensory circuits. Specifically, we found that when confined in microfluidic chambers, adult worms spontaneously transition between periods of normal activity and short quiescent bouts, with behavioral state transitions occurring every few minutes. This quiescent state, which we call Sleep, meets the behavioral requirements of C. elegans sleep, is dependent on known sleep-promoting neurons ALA and RIS, and is associated with a global down-regulation of neural activity. Consistent with prior studies of C. elegans sleep, we found that Sleep is regulated by satiety and temperature. In addition, we show for the first time that quiescence can be either driven or suppressed by thermosensory input, and that animal restraint induces quiescence through mechanosensory pathways. Together, these results establish a rich model system for studying how neural and behavioral state transitions are influenced by multiple physiological and environmental conditions. Significance StatementUnique brain states govern animal behaviors like sleep and wakefulness; however, how the brain regulates these dramatic state transitions is not well understood. Brain activity can be influenced by a complex interaction between sensory circuits that monitor the external environment, neural circuits that control behavior, and internal chemical signaling. Here, we describe a platform to study behavioral states in a context that allows us to record whole-brain activity while controlling the environment and monitoring animal behavior. Specifically, we identify a pattern of sleep bouts in the roundworm C. elegans that occur when they are confined to microscopic fluidic chambers. This behavior platform provides a powerful system to study how neural circuits interact with chemical signaling to drive brain state transitions.