How do rods and cones signal light information for non‐image‐forming visual functions?

Abstract

In the mammalian retina, an unusual class of photoreceptive neurons exists in the ganglion cell layer. These retinal ganglion cell photoreceptors express melanopsin, an opsin-like protein. It is now well established that rods/cones and the melanopsin-containing intrinsically photosensitive retinal ganglion cells (also known as ipRGCs) account for all light responses in the mammalian retina. In animals where the melanopsin protein is ablated, rods/cones are partially capable of signaling light information for non-image forming (NIF) functions such as pupillary light reflex (PLR), masking and circadian photoentrainment despite the loss of the intrinsic photosensitivity of the ipRGCs. Since the melanopsin cells are ganglion cells, rods/cones could still be signaling light information to the brain for NIF functions specifically through the melanospsin ganglion cells. To determine how rods/cones compensate for the absence of the melanopsin protein, we decided to eliminate not only the intrinsic photosensitivity of melanopsin cells, but, the cells themselves. We achieved this by incorporating the A subunit of the diphtheria toxin (DTA) specifically under the control of the melanopsin promoter. We found that, melanopsin cells are selectively ablated by the DTA toxin. In the melanopsin-DTA animals, we found several major defects in the ability of animals to detect light for PLR, masking and circadian photoentrainment. Interestingly, light functions that are not dependent on melanopsin cells, were intact in the melanopsin-DTA mice. Therefore, we conclusively showed that rods and cones require melanopsin cells to signal light information to the brain for NIF. These results demonstrate that melanopsin maybe a dedicated system for signaling light for several key non-image functions, both through its intrinsic light responses and by relaying rods/cones light information to the brain.