Technological advances in gene and cell therapies, retinal prostheses, and chemical photoswitches all show promise for restoring sight to the blind; however an accurate understanding of the functional role of each of the different types of retinal ganglion cells (RGCs) in human behavior is key to realizing the potential for these therapeutic approaches. The long-term goal of the Neitz labs is to understand all the circuitry responsible for human vision using the non-human primate as a model. As a step toward achieving that goal, this proposal focuses on the circuitry involving RGCs that receive input from short wavelength (S) cones. Color vision has served as a premier example of a success in understanding the biological underpinnings of perception. While the characteristics of the cones and the spectral sensitivities of the photopigments and their importance for trichromatic color vision are understood in detail, understanding of how the outputs of the cones are processed to give rise to perceptions is still far from complete. The S-cone pathways play a role in the conscious perception of all hues and supply retinal ganglion cells (RGCs) with important information regarding color for circadian rhythms. Based on the long known discrepancies between primate retinal physiology and human color perception, and on new data from the Neitz lab, the Neitz's hypothesize that S-cone input to hue perception is present both in the blue-yellow and red-green systems. The model makes specific predictions regarding the activities in midget ganglion cells in response to selective activation of S cones, including that midget ganglion cells receiving S cone input would not respond to white-dark edges and in this manner would differ from the conventional L vs. M midget ganglion cells that do respond well to white-dark boundaries. To test predictions of this model, I propose the following specific aim: Specific Aim 1: Optically record and analyze the activity of RGCs receiving S cone input in primate retina by using the biosensor ArcLight introduced by viral mediated gene delivery. The complete circuitry for processing S cone signals will be worked out using a custom visual stimulus to activate only S cones. ArcLight labeled neurons receiving S cone input will change in fluorescence intensity.