Development of Circadian Circuitry Underlying Feeding-Fasting Rhythms in Drosophila Larvae

Abstract

Many organisms do not exhibit strong daily behavioral rhythms early in life. The consolidation of sleep and feeding to specific times of the day does not emerge until later in development. Disruptions to circadian behaviors in early life can lead to dysregulation of both neural development and metabolic homeostasis. However, the circuit mechanisms regulating feeding rhythm development are unknown. Here, we characterize the neural circuitry responsible for driving the development of feeding-fasting rhythms in early 3rd instar (L3) Drosophila larvae. We find that inactivation of both larval s-LNv circadian pacemaker neurons and SIFamide (SIFa) neurons in the pars intercerebralis disrupts feeding rhythm development. Additionally, our data indicate feeding rhythms likely emerge due to circuit connections forming between s-LNvs and SIFa neurons at the L3 stage. Finally, we show that reductions in signaling between s-LNv and SIFa neurons interfere with normal behavioral rhythm development in L3. Specifically, RNA interference-induced reductions in pigment-dispersing factor (pdf) signaling and SIFa signaling disrupt diurnal differences in both feeding and sleep, resulting in a loss of behavioral rhythms. Altogether, our findings identify for the first time the clock and clock output circuitry responsible for feeding rhythm regulation in developing organisms.