PDF Cells Are a GABA-Responsive Wake-Promoting Component of the Drosophila Sleep Circuit

The daily sleep cycle in humans and other mammals is driven by a complex circuit within which GABAergic sleep-promoting neurons oppose arousal systems. The latter includes the circadian system, aminergic/cholinergic systems as well as neurons secreting the peptide orexin/hypocretin, which contribute to sharp behavioral transitions (Lu and Greco, 2006). Drosophila sleep has recently been shown also to be controlled by GABAergic inputs, which act on unknown cells expressing the Rdl GABAA receptor (Agosto et al., 2008). We identify here the relevant Rdl-containing cells as a subset of the well-studied Drosophila circadian clock neurons, the PDF-expressing small and large ventral lateral neurons (LNvs). LNv activity regulates the total amount of sleep as well as the rate of sleep onset, and both large and small LNvs are part of the sleep circuit. Flies mutant for either the pdf gene or its receptor are hypersomnolent, and PDF acts on the LNvs themselves to control sleep. These features of the Drosophila sleep circuit, GABAergic control of sleep onset and maintenance as well as peptidergic control of arousal, support the idea that features of sleep circuit architecture as well as the mechanisms governing the behavioral transitions between sleep and wake are conserved between mammals and insects.