Cellular damage, including wounding, drives C. elegans stress-induced sleep.

Across animal phyla, sleep is associated with increased cellular repair, suggesting that cellular damage may be a core component of sleep pressure. In support of this notion, sleep in the nematode Caenorhabditis elegans can be triggered by damaging conditions, including noxious heat, high salt, and ultraviolet light exposure. It is not clear, however, whether this stress-induced sleep (SIS) is a direct consequence of cellular damage, or of a resulting energy deficit, or whether it is triggered simply by the sensation of noxious conditions. Here, we show that thermosensation is dispensable for heat-induced sleep, that osmosensation is dispensable for salt-induced sleep, and that wounding is also a sleep trigger, together indicating that SIS is not triggered by sensation of noxious environments. We present evidence that genetic variation in cellular repair pathways impacts sleep amount, and that SIS involves systemic monitoring of cellular damage. We show that the low-energy sensor AMP-activated protein kinase (AMPK) is not required for SIS, suggesting that energy deficit is not the primary sleep trigger. Instead, AMPK-deficient animals display enhanced SIS responses, and pharmacological activation of AMPK reduces SIS, suggesting that ATP-dependent repair of cellular damage mitigates sleep pressure.

NPR-1 Modulates Plasticity in C. elegans Stress-Induced Sleep.

Sleep is beneficial yet antagonistic to critical functions such as foraging and escape, and we aim to understand how these competing drives are functionally integrated. C. elegans, which lives in reduced oxygen environments, engages in developmentally timed sleep (DTS) during larval stage transitions and engages in stress-induced sleep (SIS) during recovery from damaging conditions. Although DTS and SIS use distinct mechanisms to coordinate multiple sleep-associated behaviors, we show that movement quiescence in these sleep states is similarly integrated with the competing drive to avoid oxygen. Furthermore, by manipulating oxygen to deprive animals of SIS, we observe sleep rebound in a wild C. elegans isolate, indicating that sleep debt accrues during oxygen-induced SIS deprivation. Our work suggests that multiple sleep states adopt a common, highly plastic effector of movement quiescence that is suppressed by aversive stimuli and responsive to homeostatic sleep pressure, providing a limited window of opportunity for escape.

Food-Dependent Plasticity in Caenorhabditis elegans Stress-Induced Sleep Is Mediated by TOR-FOXA and TGF-ß Signaling.

Behavioral plasticity allows for context-dependent prioritization of competing drives, such as sleep and foraging. Despite the identification of neuropeptides and hormones implicated in dual control of sleep drive and appetite, our understanding of the mechanism underlying the conserved sleep-suppressing effect of food deprivation is limited. Caenorhabditis elegans provides an intriguing model for the dissection of sleep function and regulation as these nematodes engage a quiescence program following exposure to noxious conditions, a phenomenon known as stress-induced sleep (SIS). Here we show that food deprivation potently suppresses SIS, an effect enhanced at high population density. We present evidence that food deprivation reduces the need to sleep, protecting against the lethality associated with defective SIS. Additionally, we find that SIS is regulated by both target of rapamycin and transforming growth factor-ß nutrient signaling pathways, thus identifying mechanisms coordinating sleep drive with internal and external indicators of food availability.