If therapeutic approaches are to provide meaningful vision, it is essential that we investigate and discover the links between human perception and the activity of neurons and circuits in the visual system. Here we propose to study circuits involving S-cone pathways in primates as a model for how the visual system is organized to serve diverse functions. Much of the effort in trying to understand the biology of the primate visual system has emphasized its role in perception, in particular with producing an internal visual representation of the outside world and the objects and events within it. However, comparative studies of more primitive visual systems indicate that vision did not originally evolve as a system for perceiving the world. Rather, the visual systems of lower vertebrates emphasize neural circuitry for directly triggering movements, moment-to-moment, in real time and pathways serving non-image forming functions such as circadian photoentrainment. Our visual system has maintained evolutionarily ancient functions that are not directly involved in conscious perception. Attempts to understand the biology of vision in primates (including humans) that have failed to recognize that much of the visual system is not concerned with perception have limited our understanding of how the neural pathways comprising the visual system are organized. Theories of blue-yellow color vison in primates have focused on the classic ?blue-ON? neuron, the small bistratified retinal ganglion cell. However, evidence has accumulated that these cells may not be directly involved in the conscious perception of blue and yellow hues; rather they are well suited for triggering spatially directed movements. As an alternative to the idea that small bistratified ganglion cells are the basis for blue-yellow sensations, we have made discoveries that point to previously unknown circuitry that may have evolved only in primates specifically for conscious color perception. The goal of the experiments proposed here is to understand how S-cone pathways in primates are organized to serve the diversity of functions of the visual system including non-image forming vision functions and the largely separate functions of constructing a perceptual representation of the world vs. controlling goal-directed actions. We propose two specific aims:
Specific Aim 1 : To work out the diversity of parallel pathways for processing of signals from S cones in the primate retina using Serial Block Face Scanning Electron Microscopy.
Specific Aim 2 : To use a combination of whole-cell and loose patch recording in combination with pharmacological manipulation of specific synaptic elements to directly measure the spatio-chromatic organization of the receptive fields of ganglion cells in the primate retina that process signals from S cones, and to correlate the results to those obtained from anatomical characterization of S-cone pathways.

Public Health Relevance

Technological advancements in stem cells, gene therapy, and retinal prostheses show great promise for restoring or providing new light sensitivity to retinas of the blind; however, understanding of the basic circuitry for daylight vision lags behind the technology to provide light sensitivity. There is an urgent need to elucidate the circuitry of visual pathways and to understand their role in visual perception in order to identify the best therapeutic strategies and the most effective implementations of them.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
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Greenwell, Thomas
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University of Washington
Schools of Medicine
United States
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Schmidt, Brian P; Sabesan, Ramkumar; Tuten, William S et al. (2018) Sensations from a single M-cone depend on the activity of surrounding S-cones. Sci Rep 8:8561