Abstract
Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a recently discovered class of photoreceptors in the mammalian eye. They are essential for the entrainment of circadian rhythms to the day-night cycle. They also drive other reflexive responses to environmental lighting, including adjustments of pupil size, regulation of the hormone melatonin, and alterations in alertness. I will summarize some of the peculiar physiological features of these cells, such as their ability to stably encode retinal irradiance during prolonged illumination. I will summarize what is known about the phototransduction process in these neurons, which begins with the absorption of light by the specialized photopigment melanopsin. The downstream signaling cascade is radically different from that in rods and cones and resembles instead that in invertebrate photoreceptors. I will discuss recent evidence from our lab and others for at least four types of ipRGCs, differing in morphology, melanopsin abundance, sensitivity, and patterns of projection to the brain. I will discuss our collaborative work with the labs of Samer Hattar and Glen Prusky showing that some of the newly discovered varieties of ipRGCs project to the form vision circuits of the brain, and that they can support crude pattern vision in the absence of rods and cones. I will also discuss surprising new developments in our understanding of the synaptic circuits interconnecting ipRGCs with other retinal neurons. In particular, it now appears that these cells receive influences from classical photoreceptors through a circuit that violates a longstanding dogma about the anatomical segregation of the ON and OFF channels. Functionally, this circuit provides input from the most sensitive rod pathway, and is presumably the main route for rod influence on the circadian and pupillary systems. I will also review new evidence, developed in collaboration with the laboratories of Doug McMahon and Gary Pickard, that ipRGCs make output synapses onto dopaminergic amacrine cells, through which they are in a position to modulate the adaptation state and circadian rhythms of the retina as a whole.