Sunday, May 11, 2025
5/11/2025
Influence of retinal ganglion cells on visual neuron identity in superior colliculus - ABSTRACT The human brain is capable of making astoundingly complex computa8ons thanks in large part to the diversity of specialized neurons that are op8mized to processes discrete bits of informa8on. For example, in the visual system, different subtypes of neurons are tuned to dis8nct aspect of the visual scene, such as mo8on, color or contrast. Decades of elegant work has defined the subclasses in many ways, using func8onal, morphological, and molecular criteria. However, we have a poor understanding of how such diversity arises in the developing visual system, crea8ng a roadblock to the development of regenera8ve strategies to restore vision aCer loss due to disease or trauma8c injury. To address this gap, we will focus on the mouse superior colliculus (SC) in this proposal, which we posit is a tractable model to begin to tackle this complex problem. Previous studies have iden8fied transcrip8on factors required for SC neurogenesis and paKerning, leading to the view that intrinsic gene8c mechanisms underlie fate specifica8on in the SC. However, very few molecules have been iden8fied to have this role in comparison to other visual regions (e.g. re8na or visual cortex); and, our previous and preliminary data challenge this no8on, revealing a poten8al role for re8nal ganglion cells (RGCs) innerva8ng the SC in fate specifica8on. To test this exci8ng possibility, we will take complementary gain- and loss-of-func8on approaches, leveraging unique gene8c tools that allow us to rearrange the organiza8on of RGC inputs to the SC and follow gene8cally-defined neuronal popula8ons in different contexts. Furthermore, by combining morphological analyses of individual neurons, single nucleus RNA sequencing, and cell-specific in vivo optogene8cs with visual tuning analysis, we will comprehensively test our hypothesis. In Aim 1, we will directly determine the role of re8nal input by examining neuronal morphology of (Aim 1A) and the transcrip8onally-defined cellular diversity (Aim 1B) of SC neurons from control and enucleated mice. In Aim 2, we will leverage a unique mouse model in which the projec8ons of Islet2+ and Islet2- RGCs are segregated into different domains in the SC. Previously, we showed that visual func8on was divergent in these regions, sugges8ng poten8al switching of neuronal iden8ty. To test this possibility, we will determine the visual tuning proper8es (Aim 2A), morphology (Aim 2B), and transcriptome (Aim 2C) of gene8cally- defined SC neuron popula8ons in Islet2+- and Islet2--RGC innervated regions of the SC. Taken together, these experiments will significantly advance our understanding of the mechanisms by which cellular diversity is generated in the SC and uncover a poten8ally paradigm-shiCing role for extrinsic synap8c inputs in shaping neuronal iden8ty.
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