Partial input loss differentially modifies neural pathways

Following input loss from degeneration, injury, and/or aging, downstream circuits undergo modifications that can impact fundamental sensory computations. Using the retina to leverage known cell types, well-defined circuitry, and molecular tools, we show how multiple pathways adjust their functional properties differently to common input loss and further locate these changes within each pathway. Specifically, we asked if two OFF ganglion cell types, alpha OFF-sustained (A _OFF-S ) and OFF-transient (A _OFF-T ) cells, and their respective dominant presynaptic partners, type 2 and type 3a cone bipolar cells, respond differentially to partial cone loss. We find that A _OFF-T ganglion cells exhibit more circuit changes than A _OFF-S ganglion cells, resulting in altered spatiotemporal tuning following partial cone loss. We show that the underlying mechanisms include changes in glutamatergic, GABAergic, and glycinergic circuits in the pathway of A _OFF-T ganglion cells. In response to common input loss, our study finds different locations of circuit modifications across OFF pathways. These distinct functional changes in two pathways contribute to maintaining perceptually relevant information, preserving key visual features despite input loss. These findings provide insight into how sensory systems can compensate to ultimately serve vision.