Neuropeptide dynamics coordinate layered plasticity mechanisms adapting Drosophila circadian behavior to changing...

The Drosophila brain contains distinct circadian oscillators responsible for generating the morning and evening bouts of locomotor activity in light-dark cycles. We lack a mechanistic understanding of how environmental changes reshape the resulting bimodal rest-activity pattern. Here, we uncover a seasonal switch mechanism that remodels the evening bout of activity. Under temperate summer-like conditions, levels of the pigment-dispersing factor (PDF) neuropeptide diminish, triggering a cascade. Lowered PDF receptor (PDFR) signaling disinhibits glycogen synthase kinase 3/SHAGGY to advance the evening output, and in parallel, weakens the siesta-promoting vcDN1p-SIFamide axis to expand the evening peak. Under these conditions, vcDN1p takes over the evening pacemaker role by exerting control over the dorsal lateral oscillator neurons. Our findings elucidate how environment-induced changes in PDFR signaling tip the balanced output of the clock network, aligning daily rhythms with seasonal time. Neuropeptide-driven parallel adjustment of clock circuitry and clock protein functioning likely represents a conserved strategy, enabling animals to adapt their daily behavior to seasonal changes.