Distinctive properties of cones in the retinal clock and the circadian system

Abstract Multiple circadian clocks dynamically regulate mammalian physiology. In retina, rhythmic gene expression serves to align vision and tissue homeostasis with daily light changes. Photic input is relayed to the brain to entrain the master circadian clock, the suprachiasmatic nucleus, which matches behaviour to environmental changes. Circadian organization of the mouse retina involves coordinated, layer-specific oscillators, but so far little is known about the cone photoreceptor clock and its role in the circadian system. Using the cone-only Nrl-/- mouse model we show that cones contain a functional self-sustained molecular clockwork. By bioluminescence-combined imaging, we also show that cones provide substantial input to the retinal clock network. Furthermore, we found that light entrainment and negative masking in cone-only mice are subtly altered and that constant light displayed profound effects on their central clock. Thus, our study demonstrates the contribution of cones to retinal circadian organisation and their role in finely tuning behaviour to environmental conditions.