Partial Cone Loss Triggers Synapse-Specific Remodeling and Spatial Receptive Field Rearrangements in a Mature Retinal Circuit

Abstract

Summary: Resilience of neural circuits has been observed in the persistence of function despite neuronal loss. In vision, acuity and sensitivity can be retained after 50% loss of cones. While neurons in the cortex can remodel after input loss, the contributions of cell-type-specific circuits to resilience are unknown. Here, we study the effects of partial cone loss in mature mouse retina where cell types and connections are known. At first-order synapses, bipolar cell dendrites remodel and synaptic proteins diminish at sites of input loss. Sites of remaining inputs preserve synaptic proteins. Second-order synapses between bipolar and ganglion cells remain stable. Functionally, ganglion cell spatio-temporal receptive fields retain center-surround structure following partial cone loss. We find evidence for slower temporal filters and expanded receptive field surrounds, derived mainly from inhibitory inputs. Surround expansion is absent in partially stimulated control retina. Results demonstrate functional resilience to input loss beyond pre-existing mechanisms in control retina. : Care et al. find that photoreceptor ablation causes structural rearrangement of bipolar cell input synapses while output synapses endure. Functionally, recipient ganglion cells show altered receptive field sizes, an effect not seen after partial stimulation of control retina, demonstrating de novo changes that occur in inhibitory circuitry after photoreceptor loss. Keywords: synapse disassembly, neurodegeneration, plasticity, vision, resilience, circuit, retina, photoreceptors, bipolar cells, ganglion cells