Flipping the sleep switch

Abstract

M any people have nodded off during a long road trip, or lain in bed desperately trying to fall asleep. These experiences illustrate real-world conse-quences of an improperly maintained balance between sleep-and wake-promoting neural circuits. In a paper online in Nature, Pimentel et al. 1 describe the identification of a bona fide molecular switch that allows wake-promoting signals to turn off individual sleep-promoting neurons to regulate waking. These find-ings open up avenues for understanding the complexity of sleep regulation in healthy individuals and during disease. Multiple sleep and wake circuits are found throughout the mammalian central nervous system and are believed to interact in a mutually inhibitory manner 2,3 . A similar organization is found in the fruitfly Drosophila, in which inde-pendent sleep and wake centres cooperate to produce stable sleep and wake patterns. Flies are less complex than mammals, and their neu-ronal circuits can be easily manipulated using genetic tools, making them more tractable as study subjects. Perhaps the best-characterized sleep centre in flies is composed of neurons that project into a brain region called the dorsal fan-shaped body (dFB) 4–6