A sleep state during C. elegans development

Abstract

Caenorhabditis elegans is the simplest animal shown to sleep. It sleeps during lethargus, a larval transition stage. Behavior during lethargus has the sleep properties of a specific quiescent posture and elevated arousal threshold that are reversible to strong stimulation and of increased sleep drive following sleep deprivation. Genetic similarities between sleep regulation during C. elegans lethargus and sleep regulation in other animals point to a sleep state that was an evolutionarily ancestor to sleep both in C. elegans and other animals. Recent publications have shed light on key questions in sleep biology: First, How is sleep regulated? Second, How is sensory information gated during sleep? Third, How is sleep homeostasis mediated? Fourth, What is the core function of sleep?

Figure 1

A proposed model for the regulation of sleep during lethargus. Sleep-like quiescence occurs at larval transitions and is followed by ecdysis, the escape from the former stage cuticle. LIN-42/PERIOD sets the timing of lethargus quiescence by activating ALA and other sleep-promoting cells and by inhibiting wake-promoting cells. ALA and other sleep-promoting cells signal to sensory neurons leading to sensory gating which involves an increase in PKG and Notch activity, and decreased calcium. Hatched lines denote direct or indirect connections. Arrows denote activating interactions while perpendicular bars denote inhibitory interactions. The cellular site in which PKA promotes wake is not yet known. The source of EGF that regulates ALA is also unknown.