Classification and analysis of retinal interneurons by computational structure under natural scenes

Inhibitory neurons are diverse across the brain, but for the visual system we lack the ability to functionally classify these neurons under complex natural stimuli. Here we take the approach of classifying retinal amacrine cell responses to natural scenes using optical recording and an interpretable neural network model. We fit mouse amacrine cell responses to a two-layer convolutional neural network model of a class shown previously to accurately capture salamander ganglion cell responses to natural scenes. Using an approach from interpretable machine learning, we determined for each stimulus the model interneurons that generated each amacrine response, analogous to the set of bipolar cells that target the amacrine population.

From this analysis we clustered amacrine cells not by their natural scene responses, but by the model presynaptic neurons that constructed those responses, conservatively finding approximately seven groups by this approach. By analyzing the set of model presynaptic input neurons for each amacrine cluster, we find that distributed rather than dedicated inputs generate natural scene responses for different amacrine cell types. Additional analyses revealed distinct transient and sustained modes exhibited by the network during the response to simple flashes. These results give insight into the computational structure of how the diverse amacrine cell population responds to natural scenes, and generate multiple quantitative hypotheses for how synaptic inputs generate those responses.