Non-image-forming ocular photoreception in vertebrates

Abstract

It has been accepted for a hundred years or more that rods and cones are the only photoreceptive cells in the retina. The light signals generated in rods and cones, after processing by downstream retinal neurons (bipolar, horizontal, amacrine and ganglion cells), are transmitted to the brain via the axons of the ganglion cells for further analysis. In the past few years, however, convincing evidence has rapidly emerged indicating that a small subset of retinal ganglion cells in mammals is also intrinsically photosensitive. Melanopsin is the signaling photopigment in these cells. The main function of the inner-retina photoreceptors is to generate and transmit non-image-forming visual information, although some role in conventional vision (image detection) is also possible.

Figure 1

Schematic showing the synaptic circuitry of primate melanopsin-expressing RGCs in the retina. Melanopsin-expressing RGCs (MGs) are primarily (~95% in rodents, ~60–70% in primates) located in the ganglion cell layer, and the rest (~5% in rodents, ~30–40% in primates) are displaced to the inner nuclear layer (INL) (H-W Liao, unpublished; [17••,26]). MGs have sparse dendrites and extremely large dendritic fields. The dendrites arborize in the inner plexiform layer (IPL), forming a major (both in rodents and in primates) plexus in the outermost boundary of the IPL and a minor (even less prominent in rodents) plexus in the innermost boundary of the IPL. In primates, green and red cones provide excitatory inputs through bipolar cells to MG proximal dendrites [17••,60], and rods provide excitatory inputs through, presumably, rod bipolar cells, AII amacrine cells, and cone bipolar cells successively. Blue cones provide inhibitory inputs [17••], presumably through cone bipolar cells and inhibitory (probably GABAergic) amacrine cells [60,67]. Some amacrine cells of unknown identity also make synaptic contacts with MG somata [60]. Inset (adapted with permission from Nature [17••] copyright 2005 Macmillan Publishers Ltd; http://www.nature.com/): top panel shows the response of a primate MG cell to a 470 nm light pulse. The cell continued to fire action potentials for 30 s after the end of the light stimulus. White line shows membrane potential values averaged over 0.5 s sliding time windows. Bottom panel shows the first 5 s of the response shown on top panel. Abbreviations: +, excitatory input; −, inhibitory input; resistor symbol, electrical coupling; A, amacrine cell; AII, Type II amacrine cell; BC, blue cone; C, cone; CB, cone bipolar cell; GC, green cone; GCL, ganglion cell layer; INL, inner nuclear layer; IPL, inner plexiform layer; MG, melanopsin ganglion cell; NFL, nerve fiber layer; ONL, outer nuclear layer; OPL, outer plexiform layer; OS, outer segment; R, rod; RB, rod bipolar cell; RC, red cone.