Soporific signaling: how flies sleep through the night

Abstract

The mechanisms of sleep have been studied in Drosophila melanogaster, which show behaviors reminiscent of sleep in vertebrates. A new study identifies a growth factor signaling pathway involved in sleep regulation and consolidation in this model. Inhibiting this pathway causes a sleep pattern that is similar to insomnia in humans.

Figure 1

Proposed role of extracellular signal-regulated kinase (ERK) in the regulation of sleep in Drosophila. (a) Rho-mediated activation of ERK signaling increases sleep duration. During the night, Rho activation in the pars intercerebralis (PI) leads to the production and secretion of an EGFR ligand. The resulting phosphorylation of EGFR activates ERK in the tritocerebrum (TriC). Although the final targets of this signaling pathway are not known, the phosphorylated ERK seems to stay in the processes of the TriC neurons and may well regulate electrical activity and synaptic transmission in these neurons. (b) During wakefulness, Rho signaling in the PI is proposed to be downregulated, resulting in basal levels of ERK signaling. Inhibition of Rho expression in PI neurons results in decreased sleep levels, with short, fragmented sleep bouts. This observation suggests that these mutant flies have an increased need for sleep but are unable to stay asleep (making them a fly model of insomnia).