Dendrite Plasticity in the Adult Retina is Inhibited by DSCAM and Non-canonical Activity of the Cell Death Pathway Protein BAX

Abstract

Purpose : Attempts to regenerate and reconnect the damaged retina are complicated by the limited plasticity of adult retinal neurons. We tested the role of Dscam (Down Syndrome Cell Adhesion Molecule) and the cell death pathway protein BAX in the adult mouse retina and found that they act to limit the extension of dendrites and the establishment of novel synapses.

Methods : The connectivity of type 4 bipolar cell dendrites was quantified in wild type, Dscam and Bax mutant mouse models during development and in the adult retina. Targeted deletion of Bax and Dscam was performed to test the autonomy of mutant phenotypes and to target these genes after their role in normal developmental cell death is complete. The morphology of single type 4 bipolar cells and associated up and downstream circuitry was reconstructed by confocal microscopy and serial reconstruction of electron micrographs. Dendritic field size, the number of rods and cones contacted per bipolar cell, the number of ribbons contacted per cone, the establishment and maintenance of tiled dendritic patterning and axon projection patterns were quantified.

Results : An increase in the number of cone ribbons contacted by type 4 bipolar cells at individual cone terminals increased in the wild type retina up to postnatal day 30. Type 4 bipolar cells continue to project dendrite branches that contact additional ribbons in the Dscam and Bax mutant retina. This is associated with the invasion of territory occupied by adjacent type 4 bipolar cells and a loss of mosaic dendrite patterning in Dscam mutant retinas, whereas homotypic inhibition was maintained in the Bax mutant retina and increased ribbon sampling only was observed. Reconstruction of mutant electron micrographs identified an increase in dendrite branches that do not terminate at either a rod or cone in the Dscam mutant retina. Targeted deletion of Dscam or Bax in the adult retina results in an increase in the number of ribbon synapses contacted at individual cones and the invasion of dendrites into the territory occupied by neighboring cells.

Conclusions : We find that Dscam and Bax play a role in maintaining a stable dendrite connectivity pattern in the adult retina. Elimination of either factor in the adult retina results in an increase in the dendritic field size of type 4 bipolar cells and an increased number of synaptic connections made at individual cones.

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