A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis

In the fruit fly, Drosophila melanogaster, rest shares features with mammal ian sleep, including prolonged immobility, decreased sensory responsiveness and a homeostatic rebound after deprivation. To understand the molecular r egulation of sleep-like rest, we investigated the involvement of a candidat e gene, cAMP response-element binding protein (CREB). The duration of rest was inversely related to cAMP signaling and CREB activity. Acutely blocking CREB activity in transgenic flies did not affect the clock, but increased rest rebound. CREB mutants also had a prolonged and increased homeostatic r ebound. In wild types, in vivo CREB activity increased after rest deprivati on and remained elevated for a 72-hour recovery period. These data indicate that cAMP signaling has a non-circadian role in waking and rest homeostasi s in Drosophila.