Ablation of retinal horizontal cells from adult mice leads to rod degeneration and remodeling in the outer retina

Abstract

In the brain, including the retina, inter neurons show an enormous structural and functional diversity. Retinal horizontal cells represent a class of inter neurons that form triad synapses with photoreceptors and ON bipolar cells. At this first retinal synapse, horizontal cells modulate signal transmission from photoreceptors to bipolar cells by feedback and feed forward inhibition. To test how the fully developed retina reacts to the specific loss of horizontal cells, these inter neurons were specifically ablated from adult mice using the diphtheria toxin (DT)/DT-receptor system and the connexin57 promoter. Following ablation, the retinal network responded with extensive remodeling: rods retracted their axons from the outer plexi form layer and partially degenerated, whereas cones survived. Cone pedicles remained in the outer plexi form layer and preserved synaptic contacts with OFF but not with ON bipolar cells. Consistently, theretinal ON pathway was impaired, leading to reduced amplitudes and prolonged latencies in electroretinograms. However, ganglion cell responses showed only slight changes in time course, presumably because ON bipolar cells formed multiple ectopic synapses with photoreceptors, and visual performance, assessed with an optomotor system, was only mildly affected. Thus, the loss of an entire interneuron class can be largely compensated even by the adult retinal network. © 2012 the authors.