Invited Session II: Retinal Remodeling and Regeneration: Partial Cone Loss Triggers Differential Modification of Inhibition Across Retinal Pathways.

Cone loss up to 40-60% can be undetected by visual acuity or sensitivity metrics. These findings suggest that conventional diagnostics can be insensitive to cone loss below a threshold and/or that visual circuits can be resilient to cone loss up to a threshold. To distinguish between these possibilities, our lab studied the effects of partial cone loss in the mature mouse retina. We induced controlled cone loss by selectively expressing the diphtheria toxin receptor under the cone opsin promoter (cone-DTR). We examined the effects of 50% cone loss on the three of the most sensitive cell types in mouse retina: alpha ON sustained (AON-S), OFF sustained (AOFF-S), and OFF transient (AOFF-T) ganglion cells. With multiple cell types, we can discern between effects common across pathways, i.e., changes to common circuit components, and effects unique to pathways, i.e., changes to circuit components after the pathways diverge to each cell type. In AON-S ganglion cells, partial cone loss triggers inhibition to increase spatiotemporal integration, recover contrast gain, and receive increased synaptic inputs. While OFF pathways also exhibit modified spatiotemporal processing with fewer cones, the extent of functional adjustments was unique between the AOFF-S and AOFF-T. Cone loss caused differential modifications to inhibition in each of these retinal pathways. These findings demonstrate that partial cone loss induced circuitry changes after the divergence of OFF retinal pathways.