Sleep is evolutionarily conserved and essential. Yet, it is disadvantageous as it renders animals vulnerable to predation and limits other essential behaviors, such as feeding and reproduction. Thus, animals must balance their sleep drive with behaviors that ensure their survival. How this is regulated at the cellular and molecular level is largely unknown. The genetically tractable nematode, Caenorhabditis elegans, is a powerful sleep model, possessing a compact and completely mapped nervous system of only 302 neurons. Stress-induced sleep (SIS), analogous to sickness sleep of mammals, is a behavior that allows for a genetic dissection of these key questions. When C. elegans is exposed to noxious stimuli, avoidance responses are initiated, promoting their survival. However, if cellular damage is incurred SIS takes place, promoting recovery. Thus, SIS is an interesting model for identifying mechanisms underlying essential sleep/wake decisions. We conducted a forward genetic screen searching for sleep-defective mutants, and isolated a strain containing a loss-of-function allele of the gene T10E10.3, which encodes a G-protein coupled receptor (GPCR). Using CRISPR and cell-specific rescue, we find that T10E10.3 acts to inhibit the sleep-promoting RIS interneuron to promote arousal, while simultaneously signaling to multiple cells to promote sleep, including the ALA interneuron and a pharyngeal neuron called I6. Over-expression of T10E10.3 results in a profound early sleep phenotype, suggesting an imbalance in the sleep/wake mechanisms. Our data supports a model in which a single GPCR can regulate the balance between wake/sleep by functioning in an antagonistic manner in unique cell types. We propose that this allows the worm to escape harmful stimuli early and then ensures proper levels of recovery sleep once a safe environment is reached.
Support or Funding Information
National Science Foundation Grants IOS-CAREER-1845020 and DBI-MRI-1919847
