Circadian rhythms in metabolism, physiology, and behavior originate from cell-autonomous circadian clocks located in many organs and structures throughout the body and that share a common molecular mechanism based on the clock genes and their
protein products. In the mammalian neural retina, despite evidence supporting the presence of several circadian clocks regulating many facets of
retinal physiology and function, the exact cellular location and genetic signature of the
retinal clock cells remain largely unknown. Here we examined the expression of the core circadian clock
proteins CLOCK, BMAL1, NPAS2, PERIOD 1(PER1), PERIOD 2 (PER2), and CRYPTOCHROME2 (CRY2) in identified neurons of the mouse retina during daily and circadian cycles. We found concurrent
clock protein expression in most retinal neurons, including cone photoreceptors, dopaminergic amacrine cells, and
melanopsin-expressing intrinsically photosensitive
ganglion cells. Remarkably, diurnal and circadian rhythms of expression of all
clock proteins were observed in the cones whereas only CRY2 expression was found to be rhythmic in the dopaminergic amacrine cells. Only a low level of expression of the
clock proteins was detected in the rods at any time of the daily or circadian cycle. Our observations provide evidence that cones and not rods are cell-autonomous circadian clocks and reveal an important disparity in the expression of the core clock components among neuronal cell types. We propose that the overall temporal architecture of the mammalian retina does not result from the synchronous activity of pervasive identical clocks but rather reflects the cellular and regional heterogeneity in clock function within
retinal tissue.