Normal sleep bouts are not essential for C. elegans survival and FoxO is important for compensatory changes in sleep

Sleep deprivation impairs learning, causes stress, and can lead to death. Notch and JNK-1 pathways impact C. elegans sleep in complex ways; these have been hypothesized to involve compensatory sleep. C. elegans DAF-16, a FoxO transcription factor, is required for homeostatic response to decreased sleep and DAF-16 loss decreases survival after sleep bout deprivation. Here, we investigate connections between these pathways and the requirement for sleep after mechanical stress.

Reduced function of Notch ligand LAG-2 or JNK-1 kinase resulted in increased time in sleep bouts during development. These animals were inappropriately easy to arouse using sensory stimulation, but only during sleep bouts. This constellation of defects suggested that poor quality sleep bouts in these animals might activate homeostatic mechanisms, driving compensatory increased sleep bouts. Testing this hypothesis, we found that DAF-16 FoxO function was required for increased sleep bouts in animals with defective lag-2 and jnk-1, as loss of daf-16 reduced sleep bouts back to normal levels. However, loss of daf-16 did not suppress arousal thresholds defects. Where DAF-16 function was required differed; in lag-2 and jnk-1 animals, daf-16 function was required in neurons or muscles, respectively, suggesting that disparate tissues can drive a coordinated response to sleep need. Sleep deprivation due to mechanical stimulation can cause death in many species, including C. elegans, suggesting that sleep is essential. We found that loss of sleep bouts in C. elegans due to genetic manipulation did not impact their survival, even in animals lacking DAF-16 function. However, we found that sleep bout deprivation was often fatal when combined with the concurrent stress of mechanical stimulation.

Together, these results in C. elegans confirm that Notch and JNK-1 signaling are required to achieve normal sleep depth, suggest that DAF-16 is required for increased sleep bouts when signaling decreases, and that failure to enter sleep bouts is not sufficient to cause death in C. elegans, unless paired with concurrent mechanical stress. These results suggest that mechanical stress may directly contribute to death observed in previous studies of sleep deprivation and/or that sleep bouts have a uniquely restorative role in C. elegans sleep.