Abstract
Purpose :
The potential for deafferented bipolar cells to establish functional synapses with remaining or newly introduced photoreceptors in the adult mammalian retina is poorly understood. Recently we showed that deafferented rod bipolar cells in the rabbit retina restructure their dendrites to make new connections with healthy photoreceptors to restore scotopic vision. Here we test if the deafferented cone bipolar cells in the ground squirrel undergo similar restructuring. In particular, we examine if S-on bipolar cells, which make a one-to-one connection with a single S-cone, can rewire exclusively to S-cones in the adult retina.
Methods :
Photoreceptors in 100μm-wide strips were ablated in vivo by laser photocoagulation in the adult ground squirrel retina, leaving bipolar cells intact. Lesioned retinas were harvested days or months after the ablation for electrophysiology and immunohistochemistry (IHC) experiments. For IHC, retinas were stained with antibodies (PNA, S-Opsin, CtBP2, iGluR5, CD15, secretagogin, HCN4) to label photoreceptors, synaptic proteins, and cone bipolar cell types.
Results :
Dendritic tree change in deafferented bipolar cells becomes apparent within 2 weeks after photoreceptor loss and differs between cell types. Deafferented S-on bipolar cells maintain a vertical dendritic stalk terminating at the OPL but produce dendritic branches, which extend in all directions within the OPL. The new branches sometimes, but not always, terminate at an S-cone pedicle. S-on bipolar cells at the lesion edge that make contact with an S-cone are more likely to share that S-cone with another S-on bipolar cell (Student’s t test, p<0.02). Deafferented CD15-positive cells prune their dendritic trees and secretagogin-positive cells exhibit no signs of drastic restructuring. Electrophysiological experiments aimed at assessing functional connectivity of the deafferented S-cone bipolar cells are in progress.
Conclusions :
Cone bipolar cell types in the ground squirrel retina respond uniquely to deafferentation suggesting different plasticity mechanisms are available to different types of cone bipolar cells in the adult mammalian retina. Deafferented S-on bipolar cells can synapse with new S-cones. Unlike rod bipolar cells in the rabbit and mouse retina that direct their dendrites out of the lesion, S-on bipolar cells extend their atypical dendrites in all directions, indicative of a random exploration mechanism.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.