Spatial distribution and functional integration of displaced ipRGCs

Abstract

The mammalian retina contains many distinct types of ganglion cells, which form mosaics to evenly tile the retina with cells of each type at each position of the visual field. It is well known that displaced retinal ganglion cells (dRGCs) exist with cell bodies in the inner nuclear layer, along with regularly placed RGCs with cell bodies in the ganglion cell layer. A prominent example of dRGCs are M1-type intrinsically photosensitive ganglion cells (ipRGCs) which exist in various species including humans and non-human primates. Little is known, however, about their spatial relationship with regularly placed ipRGCs. Here, we identified mouse ipRGC types M1, M2, and M4/sON[a] by immunohistochemistry and light microscopy to anatomically investigate the distribution of displaced and regularly placed cells. Reconstruction of immunolabeled dendritic mosaics from M1 and sON[a] RGCs indicated that dRGCs tiled the retina evenly with their regularly placed RGC partners. Multi-electrode array recordings revealed conventional receptive fields of displaced sON[a] RGCs which fit into the functional mosaic of their regularly placed counterparts. We further analyzed the RGC distributions across complete retinas. The analysis of regularly placed M1 ipRGCs and [a]RGCs revealed distinct density gradients where [~]16% and [~]8% occurred as dRGCs, respectively. The density distributions of dRGCs showed type-specific patterns which followed neither the global density distribution of all ganglion cells nor the local densities of corresponding cell types. Our study shows that the displacement of ganglion cell bodies into the inner nuclear layer occurs in a type-dependent manner, where dRGCs are positioned to form complete mosaics with their regularly placed RGC partners. Our data suggest that dRGCs and regularly placed RGCs serve the same functional role within their corresponding population of ganglion cells. Significance statementWe applied large-scale anatomical and electrophysiological experiments in mice to show that displaced intrinsically photosensitive retinal ganglion cells (ipRGCs) complete the mosaics of their regularly placed counterparts with their dendritic trees and receptive fields. Therefore, displaced ipRGCs likely serve the same functional role as corresponding regularly placed cells. The density distributions of displaced ipRGCs showed distinct, type-specific patterns. Interestingly, they followed neither the global density distribution of all ganglion cells nor the local densities of corresponding cell types.