Neural Circuits Controlling Circadian Rhythms

A central question in the circadian biology field is how ∼24-hour oscillations of the molecular clock are translated into overt rhythms of behavior and physiology. Drosophila melanogaster is a powerful system that provided the first understanding of how molecular clocks are generated, and now the neural basis of circadian rhythms. In the Drosophila brain, there are about ∼150 clock neurons that collectively are responsible for timekeeping. This thesis addresses how time-of-day signals are transmitted from the clock neurons to output circuits that drive overt rhythms. This work used a genetic approach to identify genes and circuits that regulate two output rhythms: peripheral transcriptional rhythms and brain-controlled behavioral rhythms. We showed that a specific group of clock neurons, LNds, and neuropeptide F signaling regulate transcriptional rhythms in a peripheral tissue called the fat body. We also built on previous work to map a multisynaptic circuit that regulates behavioral rest:activity rhythms. The rest:activity circuit extends from the central clock neurons, s-LNvs, through multiple neuropeptidergic output neurons to motor centers. The circadian output circuit we have mapped not only receives circadian (time-of-day) signals but also signals that drive the need to sleep. This thesis provides neural bases for the regulation of circadian rhythms and highlights the different and intersecting circuits that ensure behavior and physiology occur at optimal times of day