The rod bipolar cell pathway contributes to surround responses in OFF retinal ganglion cells

Abstract Sensory neurons can be influenced by stimuli beyond their receptive field center, yet the mechanisms underlying this surround modulation remain poorly understood. In the retina, many OFF ganglion cells exhibit responses to ON stimulation outside their receptive field center. However, disentangling the pathways and cell types contributing to these responses has been challenging with traditional experimental approaches. Here, we combined optogenetics, two-photon holographic stimulation, and multi-electrode array recordings to identify the intermediate retinal cell types involved in this circuit. We found that the pathway formed by rod bipolar cells and AII amacrine cells—one of the primary relays of rod-driven signals under low-light conditions—plays a key role in mediating this surround modulation. Specifically, crossover inhibition exploits the same amacrine cells responsible for surround suppression to disinhibit distant ganglion cells. This suggests that the retina repurposes existing circuits for surround modulation, optimizing resources through multifunctional inhibitory pathways.