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Aaron B Simmons, Samuel Bloomsburg, Deidrie Briggs, Josh Hix, Emmalee Pecor, Samuel Billingslea, Jaime Young, Peter G Fuerst; Type 4 cone bipolar cell dendrite morphology is maintained by DSCAM and BAX in the adult mouse retina.. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© 2017 Association for Research in Vision and Ophthalmology.
During development of the mammalian retina, retinal neurons undergo a period of tremendous plasticity in which they will project out countless neurites which make precise connections permitting visual function. However, this plasticity is very limited in the adult retina, which poses a major hurdle when trying to treat those with retinal degenerative diseases. In this study, we tested the role of developmental factors required for neurite retraction and developmental cell death, Dscam and Bax, to see if they were also required for inhibition of neural plasticity within the adult in a population of cells which limit dendritic overlap, type 4 cone bipolar cells (T4 BCs).
T4 BCs were analyzed in Dscam and Bax mutant mice using a combination of immunohistochemistry (calsenilin), a fluorescent reporter (HTR:GFP), genetics (HTR:Cre x Ai9 reporter), and electron microscopy to analyze their density, spacing, dendritic overlap, single cell morphologies, connectivity, and microstructure. Additionally, T4 BCs were analyzed when conditionally targeting Dscam and Bax within T4 BCs during development using HTR:Cre, or after development was complete (at P45) using, Pou4f2:Cre.
Defects in the tiling and connectivity of T4 BCs was observed during development within Dscam mutants and when conditionally targeting Dscam with HTR:Cre. Similar defects arose after development within Bax mutants and when conditionally targeting Dscam or Bax within the adult. We found significant differences in the amount of photoreceptors contacted and the amount of contacts made per cone was increased. Additionally, the majority of dendrites in Dscam mutants ended in neither rods nor cones. The microstructure of flat contacts made at rods and contacts was normal in both Dscam and Bax mutants. Defects in tiling and connectivity were more severe in Dscam mutants and conditional knock outs (CKOs) compared to Bax mutants and CKOs.
In this study, we identify a novel role for Dscam and Bax in maintaining the connectivity of T4 BCs within the adult retina through inhibition of neural plasticity. We find Dscam to be sufficient for homotypic avoidance and dendritic tiling during development, and that eliminating Dscam or Bax in the adult retina restores neural plasticity resulting in a loss of homotypic avoidance and the birth of new connections.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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