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.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate not only image-forming vision like other ganglion cells, but also non-image-forming physiological responses to light such as pupil constriction and circadian photoentrainment. All ipRGCs respond to light through their endogenous photopigment melanopsin as well as rod/cone-driven synaptic inputs. A major knowledge gap is how melanopsin, rods, and cones differentially drive ipRGC photoresponses and image-forming vision. We whole-cell-recorded from M4-type ipRGCs lacking melanopsin, rod input, or cone input to dissect the roles of each component in ipRGCs' responses to steady and temporally modulated (≥0.3 Hz) lights. We also used a behavioral assay to determine how the elimination of melanopsin, rod, or cone function impacts the optokinetic visual behavior of mice. Results showed that the initial, transient peak in an M4 cell's responses to 10-s light steps arises from rod and cone inputs. Both the sustainability and poststimulus persistence of these light-step responses depend only on rod and/or cone inputs, which is unexpected because these ipRGC photoresponse properties have often been attributed primarily to melanopsin. For temporally varying stimuli, the enhancement of response sustainedness involves melanopsin, whereas stimulus tracking is mediated by rod and cone inputs. Finally, the behavioral assay showed that while all three photoreceptive systems are nearly equally important for contrast sensitivity, only cones and rods contribute to spatial acuity.

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.