Rod bipolar cells in the adult mammalian retina actively search for and selectively synapse with healthy rod photoreceptors

Abstract

Purpose : The adult retina is well known to be destructively plastic in response to injury or disease, however, recently we have presented evidence that the retina can regain visual sensitivity following local photoreceptor ablation. Healthy photoreceptors migrate into the lesion and make synaptic contact with the restructured dendrites of deafferented rod bipolar cells (RBCs). We investigated if RBC dendrites actively search for photoreceptors, if this search is selective in choosing synaptic partners, and if cone bipolar cells exhibit similar constructive plasticity.

Methods : Line-shaped lesions were produced in rabbits with a 532-nm laser, using beam diameter 100 μm, scanned at 1.7m/s along the 1.5mm of inferior retina. 200µm and 300µm wide lesions were made by staggering multiple scans. Bipolar cells and their synapses with photoreceptors were visualized with immunohistochemistry (PKCα, secretagogin, CtBP2 and mGluR6) and confocal Z-stacks were used for subsequent data analysis. The dendritic reach, defined as the distance between the dendritic tip and the point at which the dendrite exits the cell body, of healthy filled RBCs was compared to the reach of restructured dendrites of deafferented RBCs. A cone pedicle was termed as being ‘approached’ by a RBC if a dendrite terminated within or next to the cone pedicle.

Results : Rod bipolar cell dendrites restructure to send a single thickened dendrite out of the lesion into ribbon-rich areas. The thickened dendrites terminate in multiple mGluR6 doublet-ribbon pairs. The dendritic reach of the restructured RBCs is 40% longer than in the intact retina (p<0.01). Cone pedicles within the vicinity of restructured dendrites are not approached more often by RBC dendrites than cone pedicles in the healthy retina. Deafferented cone bipolar cells retain at least some of their fine dendrites and their dendritic network appears to be disturbed. However, we did not observe thickened cone bipolar cell processes reaching out to photoreceptors.

Conclusions : Adult RBCs retain the capacity to make new and correct synaptic connections following local photoreceptor loss. In contrast, the restructuring of the cone bipolar cell dendrites is subtler, suggesting the structural plasticity mechanisms available to adult rod and cone bipolar cells are different.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.