How rod, cone, and melanopsin photoreceptors come together to enlighten the mammalian circadian clock.

In mammals, a small number of retinal ganglion cells express melanopsin, an opsin photopigment, allowing them to be directly photoreceptive. A major function of these so-called intrinsically photosensitive retinal ganglion cells (ipRGCs) is to synchronize (entrain) endogenous circadian clocks to the external light:dark cycle. Thanks to their intrinsic light response, ipRGCs can support photoentrainment even when the other retinal photoreceptors (rods and cones) are absent or inactive. However, in the intact retina the ipRGC light response is a composite of extrinsic (rod/cone) and intrinsic (melanopsin) influences. As a result all three photoreceptor classes contribute to the retinal pathways providing light information to the clock. Here, we consider what each photoreceptor type contributes to the clock light response. We review electrophysiological and behavioral data pertinent to this question, primarily from laboratory rodents, drawing them together to provide a conceptual model in which each photoreceptor class plays a distinct role in encoding the light environment. We finally use this model to highlight some of the important outstanding questions in this field.