Genetic elimination of rod/cone coupling reveals the contribution of the secondary rod pathway to the retinal output.

In the retina, signals originating from rod and cone photoreceptors can reach retinal ganglion cells (RGCs)-the output neurons-through different pathways. However, little is known about the exact sensitivities and operating ranges of these pathways. Previously, we created rod- or cone-specific Cx36 knockout (KO) mouse lines. Both lines are deficient in rod/cone electrical coupling and therefore provide a way to selectively remove the secondary rod pathway. We measured the threshold of the primary rod pathway in RGCs of wild-type mice. Under pharmacological blockade of the primary rod pathway, the threshold was elevated. This secondary component was removed in the Cx36 KOs to unmask the threshold of the third rod pathway, still below cone threshold. In turn, the cone threshold was estimated by several independent methods. Our work defines the functionality of the secondary rod pathway and describes an additive contribution of the different pathways to the retinal output.