A novel approach to the functional classification of retinal ganglion cells
Résumé
Retinal neurons come in remarkable diversity based on structure, function and genetic identity. Classifying these cells is a challenging task, requiring multimodal methodology. Here, we introduce a novel approach for retinal ganglion cell (RGC) classification, based on pharmacogenetics combined with immunohistochemistry and large-scale retinal electrophysiology. Our novel strategy allows grouping of cells sharing gene expression and understanding how these cell classes respond to basic and complex visual scenes. Our approach consists of increasing the firing level of RGCs co-expressing a certain gene (Scnn1a or Grik4) using excitatory DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) and then correlate the location of these cells with post hoc immunostaining, to unequivocally characterize anatomical and functional features of these two groups. We grouped these isolated RGC responses into multiple clusters based on the similarity of the spike trains. With our approach, and accompanied by immunohistochemistry, we were able to extend the pre-existing list of Grik4 expressing RGC types to a total of 8 RGC types and, for the first time, we provide a phenotypical description of 14 Scnn1a-expressing RGCs. The insights and methods gained here can guide RGC classification but also neuronal classification challenges in other brain regions.