Interrelationships between Cellular Density, Mosaic Patterning, and Dendritic Coverage of VGluT3 Amacrine Cells

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.

Bax Contributes to Retinal Ganglion Cell Dendritic Degeneration During Glaucoma

“…4F, G ). Similarly, Bax -/- reduces dendritic field area of VGluT3-positive amacrine and type 7 cone bipolar cells [ 59 , 60 ]. Although Bax -/- decreases bipolar cell dendritic field area, the number of synapses with cone axons is similar to WT [ 59 ].…”

Cell numbers, cell ratios, and developmental plasticity in the rod pathway of the mouse retina

“…VGluT3 amacrine cells behave like the overlapping dendritic appendages of AII amacrine cells, modulating process branching in proportion to a three-fold increase in dendritic coverage factor in the Bax KO retina (Keeley et al, 2021). What distinguishes the AII amacrine cell, amongst those other amacrine cell types, is that it differentiates two different sets of processes, each arising at distinct developmental stages (Gamlin et al, 2020) and that behave independently when homotypic densities vary.…”

“…Amongst amacrine cell populations, the cholinergic amacrine cells do not alter their field extent or branching density when homotypic density varies across strains or through experimental manipulations (Farajian et al, 2004; Keeley et al, 2007), while dopaminergic amacrine cells do not preserve their plexus density in the presence of large variation in their numbers (Sankaran et al, 2018). VGluT3 amacrine cells behave like the overlapping dendritic appendages of AII amacrine cells, modulating process branching in proportion to a three‐fold increase in dendritic coverage factor in the Bax KO retina (Keeley et al, 2021). What distinguishes the AII amacrine cell, amongst those other amacrine cell types, is that it differentiates two different sets of processes, each arising at distinct developmental stages (Gamlin et al, 2020) and that behave independently when homotypic densities vary.…”

Retinal neurons establish mosaic patterning by excluding homotypic somata from their dendritic territory

“…Similarly, mouse and primate horizontal cells also grow dendrites that extend as far as the neighboring cell body; and they also show coordination between arbor size and soma positioning when cell numbers are varied (Reese and Keeley, 2015; Wässle et al, 2000). In addition to these two well-documented examples, dendrite-soma alignment can be appreciated for numerous mouse RGC types within the online “RGC museum” (Bae et al, 2018); and for mouse Vglut3 + amacrine cells (Keeley et al, 2021). Further anatomical analysis will be needed to show that these latter cell types indeed exhibit selective dendrite-soma alignment; however, these observations raise the possibility that such alignments may be a widespread phenomenon.…”