Spatial patterning of cholinergic amacrine cells in the mouse retina

The two populations of cholinergic amacrine cells in the inner nuclear layer (INL) and the ganglion cell layer (GCL) differ in their spatial organization in the mouse retina, but the basis for this difference is not understood. The present investigation examined this issue in six strains of mice that differ in their number of cholinergic cells, addressing how the regularity, packing, and spacing of these cells varies as a function of strain, layer, and density. The number of cholinergic cells was lower in the GCL than in the INL in all six strains. The nearest neighbor and Voronoi domain regularity indexes as well as the packing factor were each consistently lower for the GCL. While these regularity indexes and the packing factor were largely stable across variation in density, the effective radius was inversely related to density for both the GCL and INL, being smaller and more variable in the GCL. Consequently, despite the lower densities in the GCL, neighboring cells were more likely to be positioned closer to one another than in the higher-density INL, thereby reducing regularity and packing. This difference in the spatial organization of cholinergic cells may be due to the cells in the GCL having been passively displaced by fascicles of optic axons and an expanding retinal vasculature during development. In support of this interpretation, we show such displacement of cholinergic somata relative to their dendritic stalks and a decline in packing efficiency and regularity during postnatal development that is more severe for the GCL.