Rods, cones, and melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are responsible for all light detection in the mammalian retina. The rods and cones relay light information for both image- and non-image-forming functions through a multisynaptic pathway to the brain by means of retinal ganglion cells (RGCs). The ipRGCs, which are directly photosensitive and also receive synaptic input from rod-cone networks, account for a small fraction of the RGC population and project to brain regions mainly involved in processing non-image light information. To address how rod-cone information is conveyed to the brain, we genetically ablated the ipRGCs in mice. In the absence of ipRGCs, we demonstrated a severe impairment in light detection for NIF functions, while pattern vision and visuomotor functions were retained. Therefore, light signals for irradiance detection and pattern vision are separated at the retinal ganglion cell level, with ipRGCs acting as the principal conduits for NIF light detection, relaying both intrinsic (melanopsin-derived) and extrinsic (rod- and cone-derived) photic signals to the brain.

To further understand this unique class of RGCs, we generated mice that express Cre recombinase driven by the melanopsin promoter. Using reporter lines, we revealed four separate classes of ipRGCs, each with distinct morphological properties and intrinsic light response characteristics. We also showed more extensive innervation of target brain regions, including areas previously thought not to be innervated by ipRGCs. Finally, we present preliminary evidence suggesting that different ipRGC subtypes have distinct developmental and axonal targeting programs. These data support that there are physical divisions in NIF functions that are mediated by different classes of ipRGCs.

Therefore, these studies help to elucidate the pathways for signaling light information to the brain and the influences of light on irradiance-dependent behaviors as diverse as circadian photoentrainment, sleep, and learning and memory.