The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans

Abstract

In response to environments that cause cellular stress, animals engage in sleep behavior that facilitates recovery from the stress. In Caenorhabditis elegans, stress-induced sleep(SIS) is regulated by cytokine activation of the ALA neuron, which releases FLP-13 neuropeptides characterized by an amidated arginine-phenylalanine (RFamide) C-terminus motif. By performing an unbiased genetic screen for mutants that impair the somnogenic effects of FLP-13 neuropeptides, we identified the gene dmsr-1, which encodes a G-protein coupled receptor similar to an insect RFamide receptor. DMSR-1 is activated by FLP-13 peptides in cell culture, is required for SIS in vivo, is expressed non-synaptically in several wake-promoting neurons, and likely couples to a Gi/o heterotrimeric G-protein. Our data expand our understanding of how a single neuroendocrine cell coordinates an organism-wide behavioral response, and suggest that similar signaling principles may function in other organisms to regulate sleep during sickness.DOI: http://dx.doi.org/10.7554/eLife.19837.001

Satiety, Thermosensation and Mechanosensation Regulate a Spontaneous C. elegans Sleep State

“…We found that the onset, frequency, and duration of quiescent bouts in microfluidic chambers are unique compared to previously-reported sleep behaviors in adult C. elegans (Figure 1). While larval C. elegans display quiescence during lethargus [25], quiescence in adult worms occurs in only a few situations, such as after several hours of swimming [49,[51][52][53] or after exposure to extreme environmental conditions [40,44,45,54,55]. To determine how microfluidic-induced quiescence compares to the well-established "episodic behavior" that occurs in swimming animals and "stress-induced quiescence" that occurs from a 30 min heat shock, we quantified these behaviors using the same methods to analyze μSleep (Figure 1B-F).…”

“…Other well-known drivers of sleep are noxious environmental stressors, which we also tested in the context of our microfluidic chambers. Heat shock at temperatures greater than 30 °C is a common method to induce cellular stress and C. elegans sleep [34,40,44,45,54,72]. Although our standard μSleep assays were conducted at only 22 °C, we investigated whether these small changes from Tc could be a possible environmental regulator of quiescence.…”

“…Given the dependence of μSleep on satiety, temperature, and mechanical stress ( Figure 6), we hypothesized that each of these factors could act as stressors that contribute to a slowonset form of stress-induced sleep. Previously, studies of stress-induced sleep in C. elegans have reported acute and rapid sleep responses to noxious external stimuli [34,40,44,45,54,72], leading us to investigate if the slow-onset μSleep state could be weaker form of stress-induced sleep. To test this hypothesis, we assayed DAF-16::GFP animals in the identical environmental conditions shown in Figure 6.…”

Genetic sleep deprivation: using sleep mutants to study sleep functions

“…Cellular stress causes the secretion of EGF, which activates EGF receptor signaling in a neuron called ALA . EGF activation leads to the secretion of multiple neuropeptides from ALA, which have both overlapping and distinct inhibitory functions on behavioral activity by binding to downstream receptors, likely involving a diffusional mechanism . It is not yet clear whether ALA presents a sleep‐active neuron in the sense that it depolarizes specifically during a sleep bout or whether it promotes sleep by a different mechanism.…”

Whole-organism behavioral profiling reveals a role for dopamine in state-dependent motor program coupling inC. elegans

“…In addition, dopamine, tyramine, and octopamine influence behaviors associated with the presence or absence of food (Alkema et al, 2005;Chase et al, 2004;Horvitz et al, 1982;Sawin et al, 2000;Stern et al, 2017). The C. elegans sleep-like state is also strongly influenced by neuropeptides, including and ligands for the NPR-1 receptor (Choi et al, 2013;Iannacone et al, 2017;Nath et al, 2016;Nelson et al, 2014). Command-like neurons that release neuromodulators are capable of driving state changes: the serotonergic NSM neurons induce dwelling states (Flavell et al, 2013;Rhoades et al, 2019) and the peptidergic ALA neuron evokes a sleep-like state Nath et al, 2016;Nelson et al, 2014).…”