Structure and function of primate retinal circuits

PROJECT SUMMARY / ABSTRACT Visual information is transmitted from the primate eye to the brain through at least 20 distinct retinal ganglion cell (RGC) types, each of which is thought to extract specific features from the visual scene. Although the most numerically abundant primate RGC types have been well characterized, the physiological functions of a dozen or more sparse types remain unknown. These uncharacterized RGC types are likely involved in crucial visual reflexes and image-forming vision, but their sparsity has made them difficult to study. To address this knowledge gap, we recently developed a robust experimental approach to link genetically defined RGC types with their specific morphologies and physiological functions. Our approach led to the discovery of On-type direction-selective ganglion cells (On-DSGCs) in the macaque retina, a sparse but highly conserved RGC type that plays a critical role in gaze stabilization across vertebrates. Here, we will build on this discovery and leverage recent insights from comparative genomics to test our central hypothesis that sparse primate RGCs serve the same critical visual functions as their orthologous cell types in lower vertebrates. In Aim 1, we will test the hypothesis that the preferred directions. In Aim 2, we will test the hypothesis that the macaque retina contains object-motion sensitive RGCs that, like their orthologs in mouse retina, selectively express the transcription factor, RUNX1. To address these aims, we will utilize our proven multimodal approach, which combines ex vivo two photon calcium imaging to measure functional responses, with post-hoc molecular identification to link each recorded RGC type to its transcriptomic identity. Our integrated approach will reveal novel primate RGC types with complex receptive field properties that have hitherto escaped detection due to their sparsity. Moreover, understanding the correspondence between RGC types in primates and other species will permit rational application of findings from lower vertebrates to advance understanding of the primate, and by extension, the human visual system. These outcomes will be crucial to develop more realistic models of human vision and ultimately to improve diagnostics and therapeutics for retinal disease.