Interrogating Brain and Behavioral State Transitions with a Spontaneous C. elegans Sleep Behavior
Gonzales, Daniel L
Robinson, Jacob T
Doctor of Philosophy
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, termed “μSleep,” that is associated with a distinct global-brain state and regulated by both the animal’s 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 μSleep, 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 μSleep 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. Furthermore, the combination of this spontaneous sleep state with the microfluidic platform serves as a powerful method to uncover the fundamental function of invertebrate sleep using whole-brain imaging, high-throughput behavioral recordings, and longitudinal monitoring across animal lifespan. (abstract adapted from Gonzales, Zhou, & Robinson, 2019).
C. elegans; sleep; microfluidics; behavior; whole-brain imaging