Sleep-drive reprograms clock neuronal identity through CREB-binding protein induced PDFR expression

Neuronal circuits can be re-modeled by Hebbian plasticity, synaptic scaling and, under some circumstances, activity-dependent respecification of cell-surface receptors. Although the impact of sleep on Hebbian plasticity and synaptic scaling are well studied, sleep’s role in receptor respecification remains unclear. We demonstrate that high sleep-pressure quickly reprograms the Drosophila wake-promoting large-ventrolateral clock-neurons to express the Pigment Dispersing Factor receptor. The addition of this signaling input into the circuit is associated with increased waking and early mating success. The respecification of Pigment Dispersing Factor receptor in both young and adult large ventrolateral neurons requires two dopamine receptors and activation of the transcriptional regulator nejire (CREB-binding protein). These data identify receptor-respecification as an important mechanism to sculpt circuit function to match sleep levels with demand.