Partial Input Loss Differentially Modifies Neural Pathways

Abstract

Following input loss from degeneration, injury, and/or aging, downstream circuits undergo modifications that can impact neural computations. How neural computations across different pathways are affected by common input loss remain understudied. To leverage known cell types, well-defined circuitry, and molecular tools, we use the mouse retina to 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 (AOFF-S) and OFF-transient (AOFF-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 AOFF-T ganglion cells exhibit more circuit changes than AOFF-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 AOFF-T ganglion cells. In response to common input loss, our study finds different locations of circuit modifications across OFF pathways. These findings provide insight into how sensory pathways can compensate differentially to common input loss.