학술논문

Interrelationships between Cellular Density, Mosaic Patterning, and Dendritic Coverage of VGluT3 Amacrine Cells
Document Type
article
Source
Journal of Neuroscience. 41(1)
Subject
Biomedical and Clinical Sciences
Neurosciences
Eye Disease and Disorders of Vision
Underpinning research
1.1 Normal biological development and functioning
Amacrine Cells
Amino Acid Transport Systems
Acidic
Animals
Apoptosis
Cell Count
Cell Death
Chromosome Mapping
Dendrites
Female
Male
Mice
Mice
Inbred C57BL
Mice
Knockout
Neurons
Afferent
Quantitative Trait Loci
Retina
bcl-2-Associated X Protein
coverage factor
quantitative trait locus
recombinant inbred strain
regularity index
retinal mosaic
Voronoi domain
Medical and Health Sciences
Psychology and Cognitive Sciences
Neurology & Neurosurgery
Language
Abstract
Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina.