A sleep-active neuron can promote survival while sleep behavior is disturbed

Abstract

AbstractSleep is controlled by neurons that induce behavioral quiescence and physiological restoration. It is not known, however, how sleep neurons link sleep behavior and survival. InCaenorhabditis elegans, the sleep-active RIS neuron induces sleep behavior and is required for survival of starvation and wounding. Sleep-active neurons such as RIS might hypothetically promote survival primarily by causing sleep behavior and associated conservation of energy. Alternatively, RIS might provide a survival benefit that does not depend on behavioral sleep. To probe these hypotheses, we tested how activity of the sleep-active RIS neuron inCaenorhabditis eleganscontrols sleep behavior and survival during larval starvation. To manipulate the activity of RIS, we expressed constitutively active potassium channel (twk-18gfandegl-23gf) or sodium channel (unc-58gf) mutant alleles in this neuron. Low levels ofunc-58gfexpression in RIS increased RIS calcium transients and sleep. High levels ofunc-58gfexpression in RIS elevated baseline calcium activity and inhibited calcium activation transients, thus locking RIS activity at a high but constant level. This manipulation caused a nearly complete loss of sleep behavior but increased survival. Long-term optogenetic activation also caused constantly elevated RIS activity and a small trend towards increased survival. Disturbing sleep by lethal blue-light stimulation also overactivated RIS, which again increased survival. FLP-11 neuropeptides were important for both, induction of sleep behavior and starvation survival, suggesting that FLP-11 might have divergent roles downstream of RIS. These results indicate that promotion of sleep behavior and survival are separable functions of RIS. These two functions may normally be coupled but can be uncoupled during conditions of strong RIS activation or when sleep behavior is impaired. Through this uncoupling, RIS can provide survival benefits under conditions when behavioral sleep is disturbed. Promoting survival in the face of impaired sleep might be a general function of sleep neurons.Author SummaryThe sleep neuron RIS inCaenorhabditis elegansis required to induce sleep behavior and to promote survival upon stress. Here we show that RIS can provide survival benefits even when sleep is disturbed.