Bridging gap in comparative biology using the tree shrew visual system

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PROJECT SUMMARY A major dichotomy in comparative biology is the divergence of visual specializations in different species. This is prominently observed in rodents and primates - the former specialized to detect movement in low light conditions while the latter specialized to detect fine spatial patterns and color. A large body of research on these visual systems points to fundamental differences in structural, functional and genetic makeup of neural circuits in the early visual pathway. This makes it difficult to understand how different features of the visual world are selectively processed in the retina and in the brain. Achieving a comprehensive understanding of higher visual processing requires an understanding of visual processing in not just rodents and primates but also in other species. This also calls for the use of novel technologies for probing and translating findings across different visual systems. Tree shrew is a small animal at the phylogenetic midpoint of rodents and primates, with highly developed retina and visual cortex. Because of their diurnal and excellent color vision, tree shrews have been extensively used as a model system for understanding color processing in the mammalian visual system. This proposal will combine advanced techniques such as large-scale measurements of neural population activity, genetic screening and viral tracing to achieve detailed functional characterization of retinal ganglion cells and their connectivity to the LGN. In aim 1, we will use a high-density multi-electrode array for recording activity of large populations of retinal ganglion cells (RGCs), to reveal how morphologically and functionally distinct RGC types encode distinct visual features in their responses. To determine the diversity of gene expression in functionally distinct RGCs, in aim 2, we will employ high- throughput single-cell RNA sequencing of RGCs. We will also test for the presence of well-established molecular markers for RGC types, in the tree shrew retina. Finally, in aim 3, we will use viral labeling to determine the precise pattern of convergence from the retina to the LGN. By measuring the response of optogenetically stimulated RGCs, we will establish the lamina specific LGN projections of functionally distinct RGC types. These experiments will provide a comprehensive understanding of the structure and function of neural circuits in the early visual pathway, that produce distinct visual specializations in different species. This study will establish tree shrew as a model system for comparative studies on visual processing in higher mammals and provide novel insights into the pathologies of vision.