A problem at the core neuroscience research is to understand how sensory neurons are wired to detect features that aid in the organism's navigation. Vision begins with the photoreceptor mosaic, followed immediately by exquisite retinal circuitry that detects basic changes in contrast and color, at every location of an image. Beyond the retina, successive stages of visual cortex gradually integrate parallel streams of information to create tuning of increasing complexity. Visual neuroscience has been especially useful for understanding the computations performed by the cortex, partly because the early parallel pathways initiated in the retina can be stimulated in a highly controlled manner with standard visual displays. However, the field still lacks detailed mechanistic models of cortical function that are constrained by experimental data, a necessary hurdle to ultimately bridge studies of visual cortex to cortical-based pathologies. For this reason, the mouse's visual system is an important model for understanding cortical circuits; genetic tools in the mouse allow researchers unparalleled flexibility to manipulate and label specific cell-types that are known to make independent contributions to cortical function. In addition to genetic tools, the use of colored stimuli with the mouse may be especially fruitful for understanding general strategies of cortical computation. This study uses a combination of visual stimuli and knock-out mice to target subpopulations of the retina, with the overall goal of understanding how the integration of retinal populations contributes to multiple stages of processing within the visual cortex. An early goal of the proposal is to generate the first characterization of the spatio-temporal tuning in primary visual cortex (V1), as a function of the distribution of cone inputs from the retina. This characterization is necessary to leverage future studies of parallel processing streams in the mouse visual cortex, such as ours. It will also test the hypothesis that color is encoded independently of the spatial and dynamic patterns of a visual scene. In the next aim, we will measure fundamental principles of cortical wiring by testing the hypothesis that V1 color tuning is shaped by systematic pooling of its feedforward inputs. The alternative hypothesis is that the cortex builds hierarchies of tuning by ?random? circuits. These measurements are made possible by coarse anisotropy in the photoreceptor mosaic of mice. In the final aim, we will investigate how different visual cortical areas communicate via parallel channels. To begin, we will determine if higher visual areas are dedicated to processing specific bands of color, space, and time. This will be followed by measurements of how interneurons contribute to the cortico-cortical integration of pathways, using spatially structured optogenetics. The experimental design of the proposal relies on genetic tools, imaging, electrophysiology, optogenetics, and the functional architecture of color tuning in the mouse's visual system.
Modeling the mechanisms by which visual cortical neurons integrate inputs to produce outputs is necessary to obtain a mechanistic understanding of visual processing and also contributes more generally to understanding circuit mechanisms across all of the cerebral cortex. Deficits in central visual processing are linked to dyslexia, strabismus, and amblyopia. Furthermore, the mechanisms uncovered in visual cortex are likely to reveal general processing strategies for other cortical areas, thus having important implications for diseases such as schizophrenia and autism, where cortical-based pathologies are linked.