Correlates of sleep and waking in Drosophila melanogaster

Drosophila exhibits a circadian rest-activity cycle, but it is not known wh ether fly rest constitutes sleep or is mere inactivity. it is shown here th at, like mammalian sleep, rest in Drosophila is characterized by an increas ed arousal threshold and is homeostatically regulated independently of the circadian clock. As in mammals, rest is abundant in young flies, is reduced in older flies, and is modulated by stimulants and hypnotics. Several mole cular markers modulated by sleep and waking in mammals are modulated by res t and activity in Drosophila, including cytochrome oxidase C, the endoplasm ic reticulum chaperone protein BiP, and enzymes implicated in the catabolis m of monoamines. Flies Lacking one such enzyme, arylalkylamine N-acetyltran sferase, show increased rest after rest deprivation. These results implicat e the catabolism of monoamines in the regulation of sleep and waking in the fly and suggest that Drosophila may serve as a model system for the geneti c dissection of sleep.