Intrinsically photosensitive retinal ganglion cells (ipRGCs) are inner retinal photoreceptors that mediate non-image-forming visual functions, e.g. pupillary constriction, regulation of pineal melatonin release, and circadian photoentrainment. Five types of ipRGCs were recently discovered in mouse, but whether they exist in other mammals remained unknown. We report that the rat also has five types of ipRGCs, whose morphologies match those of mouse ipRGCs; this is the first demonstration of all five cell types in a non-mouse species. Through immunostaining and λmax measurements, we showed that melanopsin is likely the photopigment of all rat ipRGCs. The various cell types exhibited diverse spontaneous spike rates, with the M1 type spiking the least and M4 spiking the most, just like we had observed for their mouse counterparts. Also similar to mouse, all ipRGCs in rat generated not only sluggish intrinsic photoresponses but also fast, synaptically driven ones. However, we noticed two significant differences between these species. First, whereas we learned previously that all mouse ipRGCs had equally sustained synaptic light responses, rat M1 cells’ synaptic photoresponses were far more transient than those of M2–M5. Since M1 cells provide all input to the circadian clock, this rat-versus-mouse discrepancy could explain the difference in photoentrainment threshold between mouse and other species. Second, rat ipRGCs’ melanopsin-based spiking photoresponses could be classified into three varieties, but only two were discerned for mouse ipRGCs. This correlation of spiking photoresponses with cell types will help researchers classify ipRGCs in multielectrode-array (MEA) spike recordings.

SUMMARY Retinal neurons exhibit sustained vs. transient light responses, which are thought to encode low- and high-frequency stimuli respectively. This dichotomy has been recognized since the earliest intracellular recordings from the 1960s, but the underlying mechanisms are not yet fully understood. We report that in the ganglion cell layer of rat retinas, all spiking amacrine interneurons with sustained ON photoresponses receive gap-junction input from intrinsically photosensitive retinal ganglion cells (ipRGCs), recently discovered photoreceptors that specialize in prolonged irradiance detection. We have identified three morphological varieties of such ipRGC-driven displaced amacrine cells: 1) monostratified cells with dendrites terminating exclusively in sublamina S5 of the inner plexiform layer; 2) bistratified cells with dendrites in both S1 and S5; and 3) polyaxonal cells with dendrites and axons stratifying in S5. Most of these amacrine cells are wide-field, although some are medium-field. The three classes respond to light differently, suggesting they probably perform diverse functions. These results demonstrate that ipRGCs are a major source of tonic visual information within the retina and exert widespread intraretinal influence. They also add to recent evidence that ganglion cells signal not only to the brain.

Due to an author oversight during the final stages of manuscript preparation, in the version of this article originally published online, the following sentence was inadvertently omitted from the end of the first paragraph of the section ''Synaptic Mechanisms'' on the fifth page: ''By contrast, the intrinsic light responses of ipRGCs (two M1 cells, one M3 cell, one M4 cell, and two M5 cells) were not significantly affected by MFA (p = 0.09; data not shown).'' Thus, the entire paragraph in question should read:The next series of experiments investigated the mechanisms through which ipRGCs transmit photoresponses to displaced amacrine cells. Based on a previous report of tracer coupling [10], we hypothesized that our sustained amacrines received ipRGC input through electrical synapses. To test this, we isolated melanopsin-driven light responses using the glutamate blockers and added 50-100 mM meclofenamic acid (MFA) to block gap junctions [15]. All amacrine cells' (n = 11) melanopsin-mediated light responses were dramatically reduced, indicating a critical role for gap junctions (Figure 6A). By contrast, the intrinsic light responses of ipRGCs (two M1 cells, one M3 cell, one M4 cell, and two M5 cells) were not significantly affected by MFA (p = 0.09; data not shown).The article has now been updated online to include the missing sentence. The authors apologize for the inconvenience.