Influence of the rod photoresponse on light adaptation and circadian rhythmicity in the cone ERG

Purpose: In the mammalian retina, rod and cone pathways are fundamentally intertwined, with signals from both converging on cone bipolar cells to reach retinal ganglion cells. Psychophysical and electrophysiological data suggests that, as a consequence, rod signal transduction has a suppressive effect on the activity of cone pathways. It therefore might be assumed that the balance between rod and cone input to cone bipolar cells would be subject to dynamic regulation. There is evidence of light and time-of-day dependent alterations in this parameter. Here we set out to determine the extent to which such changes in rod-cone pathway convergence explain alterations in cone pathway function associated with light adaptation and circadian phase by recording cone electroretinograms (ERGs) in mice deficient in rod phototransduction. Methods: Cone-isolated ERGs elicited by bright flashes superimposed on a rod saturating background light were recorded from wild-type and rod transducin deficient (Gnat1−/−) mice. The process of light adaptation was observed by tracing changes in the ERG waveform over 20 min exposure to the background light in these genotypes, and circadian control by comparing responses at subjective midday and midnight. Results: The cone ERG b-wave exhibited significantly enhanced amplitude and reduced latency (implicit time) in Gnat1−/− mice under all conditions. Light adaptation was associated with a robust increase in b-wave amplitude in Gnat1−/− mice but, in contrast to wild types, almost no change in implicit time. Gnat1−/− mice retained circadian rhythms in the cone ERG with b-wave amplitudes larger and latencies reduced during the subjective day. Conclusions: Rod phototransduction has a strong suppressive effect on the cone ERG. Light adaptation in cone pathways relies in part on reductions in this effect, although mechanisms intrinsic to cone pathways also play an important role. Similarly, while changes in coupling between rod and cone pathways over the course of the day may contribute to circadian regulation of the cone pathway they are not sufficient to explain circadian rhythms in the wild-type cone ERG