ConeOpsinsToPercept

Vision operates across a billion-fold range of light intensities from a moonless night to a sunny beach. One mechanism contributing to this outstanding performance is the division of labor between two types of light-sensitive receptor cells, rods and cones. In dim light, vision is mediated by slow but highly sensitive rods. In brighter light, cones mediate vision with fast signal kinetics but lower sensitivity. It has been hypothesized that this division of labor corresponds to a fundamental tradeoff between sensitivity and speed common to any (man-made or biological) sensory system. However, the precise nature of this trade-off has remained unresolved, partly because changes in light levels involve fundamental changes in the neural circuits that read out and process rod and cone signals. This research plan proposes to resolve the trade-off between sensitivity and speed end-to-end from photoreceptor signal kinetics to retinal output and to visually-guided behavior with the resolution of single amino acid mutations. To address this ambitious goal, I will contribute my expertise in cone physiology and a battery of genetically modified mice in which single amino acid mutagenesis speeds-up or slows-down cone responses. The Ala-Laurila laboratory will provide the expertise and infrastructure required to causally link opsin biophysics to photoreceptor signaling, photoreceptor signaling to neural processing by the retina, and neural processing to mouse behavior and human perception. This combination of technologies and expertise is unique. As the grandson of Holocaust survivors, this proposal will enable my dream of returning to Europe to take on my first academic faculty job. Professionally, it will empower me to bridge the skills acquired during my Ph.D. to an integrative approach in neuroscience, and will allow me to form my own niche in the international scientific community.

2021

2023