Abstract
In the absence of functional rod and cone photoreceptors, mammals are able to detect light for several light-dependent physiological functions such as adjusting the circadian clock to match the solar day. The ability to detect light and regulate the phase of the circadian pacemaker is dependent on the intrinsically photosensitive retinal ganglion cells (ipRGCs) that express the photopigment melanopsin. In the absence of the intrinsic light response of ipRGCs, rods and cones together signal light input to the circadian pacemaker. Several studies have begun to address the relative contribution of each photoreceptor type to circadian photoentrainment; however, a comprehensive model for these interactions is far from complete. To address this question, we used genetic mouse models that lack functional rods, have cones as the only functional photoreceptors or have rods as the only functional photoreceptors. We demonstrate that rods are solely responsible for photoentrainment at low light intensity. Surprisingly, rods, but not cones, are predominantly responsible for light signaling for circadian functions at photopic intensities where they are bleached and hence cannot support image detection. Using animals in which cone photoreceptors are ablated, we demonstrate that rod photoreceptors contribute to circadian photoentrainment through two distinct retinal circuits that are either cone cell-dependent at high light intensity or cone cell-independent at low light intensity. These findings reveal a previously unsuspected role for rods in circadian photoentrainment and indicate that cones may have a minor role in this function.