Interpreting convolutional neural networks to study wide-field amacrine cell inhibition in the retina

Wide-field amacrine cells (ACs) play a unique role in retinal processing by integrating visual information across a large spatial area. Their inhibitory influence has been implicated in multiple retinal functions such as differential motion detection and the suppression of retinal activity during eye movements. However, a coherent understanding of their general function is lacking due to difficulties in directly recording from these cells and identifying effective visual stimuli to activate them. In this study, we used convolutional neural networks (CNNs) to investigate widefield inhibition mediated by wide-field ACs in the marmoset retina. We trained CNNs to mimic the function of the retina by predicting retinal ganglion cell (RGC) population responses to naturalistic movie stimuli and optimising the most exciting inputs (MEIs) to visualise RGCs’ receptive field (RF) structures. We then optimized suppressive surrounds beyond classical RGC RF boundaries, intended to capture the inhibitory effect of wide-field ACs on RGC activity. These optimized surrounds reduced MEI-elicited activity by 10% to 30%, demonstrating that CNNs not only mimic retinal responses but can also reveal hidden computational aspects of wide-field inhibition. However, suppression strength and generalization varied across architectures and datasets, indicating potential model-specific effects, high-lighting the importance of cautious interpretation. Overall, our approach illustrates how interpretability methods applied to artificial neural networks can offer new hypotheses regarding biological retinal computation, paving the way for targeted experimental validation. The code is available here .