Project Summary/Abstract The long-term goal of this proposal is to characterize the connectivity of specific circuits in the mouse visual system whose gross architecture is highly conserved across species from mouse to primate. The objective is to identify the neural circuits that transmit visual information from the retina, through different regions of the dorsal lateral geniculate nucleus (dLGN), to specific populations of neurons in the primary visual cortex (V1) that contribute to visual perception and behavior. The central hypotheses of this proposal are: (1) that neurons in the shell and core of the dLGN receive different types of visual information from the retina and, therefore, can transmit different types of visual information to V1 neurons; (2) The balance of core and shell input that V1 neurons receive influences their tuning properties. The experiments outlined in this proposal will test these hypotheses by pursuing three specific aims: (1) Identifying and characterizing the retinal ganglion cell (RGC) types that provide input to neurons in the core of the dLGN, as well as the neurons that those dLGN neurons contact in V1; (2) Determining whether genetically-identified neurons in V1 receive input from unique patterns of RGCs; and (3) Determining how input from neurons in the core of the dLGN influence tuning properties in genetically-identified populations of V1 neurons. This proposal is technologically innovative; it will use novel mouse lines as well as a combination of rabies circuit tracing, whole-cell recording, optogenetic stimulation, chemogenetic silencing, and two-photon calcium imaging to accomplish its aims. The proposed research will yield significant findings that will provide considerable insight into how information is encoded, processed, and ultimately transmitted throughout the mouse visual pathway. These findings are of utmost importance as the computations performed in these pathways generate a representation of the visual scene and ultimately make characteristic contributions to perception and behavior. The proposed research will also help determine the extent to which visual processing in the mouse visual system does, or does not, mimic visual processing in the primate visual system. Understanding the extent to which computations performed in the visual pathway overlap in mouse and primate visual systems is critical for determining how research done in in the mouse visual system translates to the primate — and therefore human — visual system. Indeed, to successfully develop strategies to restore sight across a wide range of afflictions of the visual system, it is critical to first understand how the visual system gives rise to our sense of the world around us. The work proposed here will unequivocally move us closer to this goal.