Sleep bouts are not essential for *C. elegans* survival, but FoxO is important for compensatory sleep

Abstract

Sleep deprivation impairs learning, causes stress, and can lead to death. *C. elegans* DAF-16, a FoxO transcription factor, is required for homeostatic response to decreased sleep and DAF-16 loss decreases survival after sleep deprivation. Previous work showed that Notch and JNK-1 signaling pathways impact *C. elegans* sleep in complex ways; these have been hypothesized to involve compensatory sleep. Here, we investigate connections between these pathways and the requirement for sleep after mechanical stress. Reduced function of the Notch ligand LAG-2 or JNK-1 kinase resulted in increased developmentally-timed sleep during transition to adulthood. But, these animals exhibited aberrantly slow responses to external stimuli only during sleep bouts. This constellation of defects suggested that poor quality sleep bouts in these animals might activate homeostatic compensatory mechanisms, which drive compensatory increased/prolonged sleep. Consistent with this hypothesis, we found that DAF-16 FoxO function was required for increased sleep in animals with defective *lag-2* and *jnk-1*, as loss of *daf-16* reduced sleep back to normal levels, without ameliorating defects in arousal thresholds during sleep bouts. 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 a coordinated behavioral response to sleep need in disparate tissues. Sleep deprivation due to mechanical stimulation can cause death in many species, including *C. elegans*. This suggested that sleep may be essential for survival. We found that loss of sleep bouts in *C. elegans* 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 confirm that *C. elegans* Notch and JNK-1 signaling are required to achieve normal sleep depth, confirm that DAF-16 is required to activate compensatory responses to inadequate/decreased sleep, and suggest that sleep bout deprivation alone does not 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.

Publication
BMC Neuroscience
Date