Nonlinear Spatial Integration Underlies the Diversity of Retinal Ganglion Cell Responses to Natural Images

How neurons encode natural stimuli is a fundamental question for sensory neuroscience. In the early visual system, standard encoding models assume that neurons linearly filter incoming stimuli through their receptive fields, but artificial stimuli, such as contrast-reversing gratings, often reveal nonlinear spatial processing. We investigated to what extent such nonlinear processing is relevant for the encoding of natural images in retinal ganglion cells in mice of either sex. We found that standard linear receptive field models yielded good predictions of responses to flashed natural images for a subset of cells but failed to capture the spiking activity for many others. Cells with poor model performance displayed pronounced sensitivity to fine spatial contrast and local signal rectification as the dominant nonlinearity. By contrast, sensitivity to high-frequency contrast-reversing gratings, a classical test for nonlinear spatial integration, was not a good predictor of model performance and thus did not capture the variability of nonlinear spatial integration under natural images. In addition, we also observed a class of nonlinear ganglion cells with inverse tuning for spatial contrast, responding more strongly to spatially homogeneous than to spatially structured stimuli. These findings highlight the diversity of receptive field nonlinearities as a crucial component for understanding early sensory encoding in the context of natural stimuli. SIGNIFICANCE STATEMENT Experiments with artificial visual stimuli have revealed that many types of retinal ganglion cells pool spatial input signals nonlinearly. However, it is still unclear how relevant this nonlinear spatial integration is when the input signals are natural images. Here we analyze retinal responses to natural scenes in large populations of mouse ganglion cells. We show that nonlinear spatial integration strongly influences responses to natural images for some ganglion cells, but not for others. Cells with nonlinear spatial integration were sensitive to spatial structure inside their receptive fields, and a small group of cells displayed a surprising sensitivity to spatially homogeneous stimuli. Traditional analyses with contrast-reversing gratings did not predict this variability of nonlinear spatial integration under natural images.