Parametric effects of light acting via multiple photoreceptor types contribute significantly to circadian entrainment in Drosophila melanogaster

Circadian rhythms in physiology and behavior have near 24-hour periodicities that must adjust to the exact 24-hour geophysical cycles on earth to ensure stable and adaptive daily timing, a phenomenon referred to as entrainment. Entrainment can either occur via instantaneous shifts in the phase of the clock, a process referred to as non-parametric entrainment, or by light acting continuously to alter the speed of the clock, a process referred to as parametric entrainment. Though typically studied in isolation, real-world entrainment involves both parametric and non-parametric processes. While Drosophila melanogaster has been a powerful model organism for understanding the molecular and neuronal underpinnings of entrainment, the vast majority of the work on entrainment in this species has focused on non-parametric light effects. Though parametric effects of light have been described for D. melanogaster, there have been few studies examining the mechanisms underlying such effects. This has been due, in large part, to the fact that the fly’s circadian system does not free-run strongly under constant light conditions, which is required to experimentally address parametric effects of light. In this study, we demonstrate that light has robust parametric effects on the Drosophila circadian clock and that the timing of daily activity is strongly influenced by these effects, even under the standard step-function light/dark cycles employed by the field. We also show that parametric effects of light depend on external photoreceptors and, to a surprising extent, on the blue light photoreceptor cryptochrome. Furthermore, we introduce ramped light cycles as an entrainment paradigm that produces entrainment features that are similar to those seen in mammalian systems, in that they eliminate the confounding effects of the large startle responses displayed by flies under step function light/dark cycles and require multiple days for re-entrainment to shifted cycles. These features make possible a new experimental approach to understanding the mechanisms underlying entrainment in the fly.