In congenital stationary night blindness, type 2 (CSNB2)—a disorder involving the Ca_v1.4 (L-type) Ca²⁺ channel—visual impairment is mild considering that Ca_v1.4 mediates synaptic release from rod and cone photoreceptors. Here, we addressed this conundrum using a Ca_v1.4 knockout (KO) mouse and a knock-in (G369i KI) mouse expressing a non-conducting Ca_v1.4. Surprisingly, Ca_v3 (T-type) Ca²⁺ currents were detected in cones of G369i KI mice and Ca_v1.4 KO mice but not in cones of wild-type mouse, ground squirrels, and macaque retina. Whereas Ca_v1.4 KO mice are blind, G369i KI mice exhibit normal photopic (i.e. cone-mediated) visual behavior. Cone synapses, which fail to form in Ca_v1.4 KO mice, are present, albeit enlarged, and with some errors in postsynaptic wiring in G369i KI mice. While Ca_v1.4 KO mice lack evidence of cone synaptic responses, electrophysiological recordings in G369i KI mice revealed nominal transmission from cones to horizontal cells and bipolar cells. In CSNB2, we propose that Ca_v3 channels maintain cone synaptic output provided that the nonconducting role of Ca_v1.4 in cone synaptogenesis remains intact. Our findings reveal an unexpected form of homeostatic plasticity that relies on a non-canonical role of an ion channel.

Animals navigate by learning the spatial layout of their environment. We investigated spatial learning of mice in an open maze where food was hidden in one of a hundred holes. Mice leaving from a stable entrance learned to efficiently navigate to the food without the need for landmarks. We developed a quantitative framework to reveal how the mice estimate the food location based on analyses of trajectories and active hole checks. After learning, the computed ‘target estimation vector’ (TEV) closely approximated the mice’s route and its hole check distribution. The TEV required learning both the direction and distance of the start to food vector, and our data suggests that different learning dynamics underlie these estimates. We propose that the TEV can be precisely connected to the properties of hippocampal place cells. Finally, we provide the first demonstration that, after learning the location of two food sites, the mice took a shortcut between the sites, demonstrating that they had generated a cognitive map.