Unraveling the role of asymmetric excitatory and inhibitory synaptic inputs to retinal ganglion cell direction selectivity.

Introduction: Understanding the mechanisms underlying direction selectivity in retinal ganglion cells (RGCs) is crucial in visual neuroscience. Retinal direction selectivity is critical for gaze stabilization through optokinetic and vestibulo-ocular reflexes, and its loss impairs the ability to stabilize gaze and track moving objects, potentially impacting behaviors that rely on accurate motion detection. The prevailing hypothesis proposes that the interplay between excitatory and inhibitory inputs is pivotal for the emergence of direction selectivity in RGCs. Methods: To dissect the contributions of these inputs, we employed dynamic-clamp recordings utilizing computationally modeled, synthetic excitatory and inhibitory conductances of varying amplitudes and time onsets in mouse RGCs. Results: The use of combinations of excitatory and inhibitory conductances with altered amplitude or timing in configurations not found in natural physiological conditions, allowed us to evaluate the specific contribution and impact of these modified components on direction selectivity. We found that asymmetries in both excitatory and inhibitory inputs are critical for the emergence of sharp directional tuning. Discussion: Our findings contribute to advance our understanding of the cellular and synaptic mechanisms that underlie retinal direction selectivity.