Activity-dependent development of synaptic circuits mediates direction selectivity in an axis-specific manner.

The optokinetic reflex (OKR), which stabilizes images on the retina as a mouse navigates its environment, originates in direction-selective ganglion cells (DSGCs). A mouse model that lacks cholinergic retinal waves, the β2-nAChR-KO mouse, does not develop horizontal direction selectivity but preserves vertical direction selectivity. Here, we demonstrate that the absence of horizontal direction selectivity in β2-nAChR-KO mice results in a loss of the OKR along the horizontal axis, consistent with previous findings on optomotor response. In addition, we observe diminished asymmetric inhibition onto horizontal-preferring DSGCs. In contrast, OKR along the vertical axis and asymmetric inhibition onto vertical-preferring DSGCs is maintained. Dual whole-cell voltage-clamp recordings show that this decrease in asymmetric inhibition is attributable to a reduction in GABAergic conductance between horizontal-preferring DSGCs and their presynaptic partner. These results indicate that, before the onset of vision, spontaneous activity selectively influences the formation of precise wiring essential for motion detection along the horizontal axis.