Organization of Retinothalamic Circuits and their Contributions to Visual Processing in Primary Visual Cortex - Project Summary/Abstract The goal of this proposal is to characterize the connectivity and functional role of specific circuits in the mammalian visual system. This proposal focuses on neural circuits that transmit visual information from retinal ganglion cells (RGCs) in the retina, through different regions of the dorsal lateral geniculate nucleus (dLGN) in the thalamus, to specific populations of neurons in the primary visual cortex (V1). The combined activity of these visual pathway circuits results in the generation of tuning properties in V1 neurons (eg. direction selectivity) that make important contributions to visual perception and behavior. The objective of this proposal is to understand how specific retino-geniculo-cortical circuits, carrying different types of visual information, influence the response properties of V1 neurons in the mouse visual system. The central hypotheses of this proposal are: (1) There are at least three distinct pathways in the dLGN carrying information from different types of motion-tuned retinal ganglion cells (mt-RGCs) and non-motion-tuned retinal ganglion cells (nmt- RGCs) to V1 neurons; (2) These pathways make unique contributions to tuning properties of V1 neurons; and (3) Motion-tuned and non-motion-tuned information originating in the retina, and delivered via the dLGN to V1 neurons, make specific contributions to the generation of tuning in V1 neurons. The experiments outlined in this proposal will test these hypotheses by pursuing three specific aims: (1) Establishing the molecular identity of the neurons that comprise these dLGN pathways, determining how inputs from mt-RGCs and nmt-RGCs are delivered to them, and identifying which neurons they contact in V1; (2) Determining how input from neurons in these dLGN pathways influence response properties in identified populations of V1 neurons; and (3) Determining the contribution that mt-RGCs and nmt-RGCs make to response properties in specific populations of V1 neurons. This proposal is technologically innovative: it will use a combination of a novel form of anterograde circuit tracing, single-cell RNA sequencing, chemogenetic silencing, and two-photon calcium imaging to accomplish its aims. The proposed research will yield significant findings answering fundamental questions about how information is encoded, processed, and ultimately transmitted throughout the pathways of the visual system. Answering these types of fundamental questions is of utmost importance because the computations performed by these pathways generate response properties in neurons that give rise to visual perception and behavior. Understanding how the visual system gives rise to our sense of the world around us is a critical first step toward successfully developing strategies to treat a wide range of diseases of the visual system. Indeed, this is the long-term goal of any visual system research program, and work proposed here will unequivocally move us closer to both of this goal.
