Voltage-gated calcium channel subunit α₂δ-3 shapes light responses of mouse retinal ganglion cells mainly in low and moderate light levels

Abstract

Little is known about the function of the auxiliary α₂δ subunits of voltage-gated calcium channels in the retina. We investigated the role of α₂δ-3 (Cacna2d3) using a mouse in which α₂δ-3 was knocked out by LacZ insertion. Behavior experiments indicated a normal optokinetic reflex in α₂δ-3 knockout animals. Strong expression of α₂δ-3 could be localized to horizontal cells using the LacZ-reporter, but horizontal cell mosaic and currents carried by horizontal cell voltage-gated calcium channels were unchanged by the α₂δ-3 knockout. In vivo electroretinography revealed unaffected photoreceptor activity and signal transmission to depolarizing bipolar cells. We recorded visual responses of retinal ganglion cells with multi-electrode arrays in scotopic to photopic luminance levels and found subtle changes in α₂δ-3 knockout retinas. Spontaneous activity in OFF ganglion cells was elevated in all luminance levels. Differential response strength to high- and low-contrast Gaussian white noise was compressed in ON ganglion cells during mesopic ambient luminance and in OFF ganglion cells during scotopic and mesopic ambient luminances. In a subset of ON ganglion cells, we found a sharp increase in baseline spiking after the presentation of drifting gratings in scotopic luminance. This increase happened after gratings of different spatial properties in knockout compared to wild type retinas. In a subset of ON ganglion cells of the α₂δ-3 knockout, we found altered delays in rebound-like spiking to full-field contrast steps in scotopic luminance. In conclusion, α₂δ-3 seems to participate in shaping visual responses mostly within brightness regimes when rods or both rods and cones are active.