Retinal innervation tunes circuits that drive nonphotic entrainment to food

Daily changes in light and food availability are major time cues that influence circadian timing¹. However, little is known about the circuits that integrate these time cues to drive a coherent circadian output^1-3. Here we investigate whether retinal inputs modulate entrainment to nonphotic cues such as time-restricted feeding. Photic information is relayed to the suprachiasmatic nucleus (SCN)-the central circadian pacemaker-and the intergeniculate leaflet (IGL) through intrinsically photosensitive retinal ganglion cells (ipRGCs)⁴. We show that adult mice that lack ipRGCs from the early postnatal stages have impaired entrainment to time-restricted feeding, whereas ablation of ipRGCs at later stages had no effect. Innervation of ipRGCs at early postnatal stages influences IGL neurons that express neuropeptide Y (NPY) (hereafter, IGL^NPY neurons), guiding the assembly of a functional IGL^NPY-SCN circuit. Moreover, silencing IGL^NPY neurons in adult mice mimicked the deficits that were induced by ablation of ipRGCs in the early postnatal stages, and acute inhibition of IGL^NPY terminals in the SCN decreased food-anticipatory activity. Thus, innervation of ipRGCs in the early postnatal period tunes the IGL^NPY-SCN circuit to allow entrainment to time-restricted feeding.