Abstract
Retinal ganglion cells have traditionally been grouped into cells that are sensitive to luminance but not spatial structure and cells with responses that are enhanced by spatial structure. Neither category captures responses of mouse Off Transient alpha cells, which are largest for spatially homogeneous inputs and are suppressed by spatial structure. We identified two circuit mechanisms that together can explain this unusual spatial selectivity. First, inhibition to these cells is tuned to finer spatial structure than excitation, causing the balance of excitation and inhibition to depend on spatial scale. Second, the excitatory synapses onto these cells undergo strong synaptic depression and the modulation of that depression by presynaptic inhibition amplifies responses to the transition from spatially structured to homogeneous inputs. A spatiotemporal computational model incorporating these circuit features quantitatively recapitulates the observed dynamics. These findings reveal how localized inhibition and short-term plasticity jointly create the distinctive spatial selectivity of Off Transient cells.