The retina is a complex neural tissue whose continued correct functioning is essential to vision. Because it is subject to both developmental and acquired dysfunction, objective methods are necessary to diagnose and investigate its functional disorders. A method that holds great promise is examination of the electroretinogram (ERG), a gross electrical signal that can be recorded non-invasively and reflects activity of all retinal cells. To realize the full potential of the ERG it is necessary to know how to analyze the recordings to provide quantitative information about the different retinal mechanisms that contribute to it. The proposed experiments will be carried out in anesthetized animals: a primate (macaca mulatta) whose retina is very similar that of humans, and mice where genetically manipulated retinas are available. The overall goals of the research are 1) to clarify the cellular origins of the components of the scotopic and photopic ERG 2) to construct models that provide a quantitative description of the contribution of each component to the ERG flash response, for stimuli of any strength, and under any condition of light-adaptation 3) to use the ERG to investigate mechanisms of photon signaling and network light adaptation in the intact mammalian retina. Isolation of components using specific stimulus paradigms and invasive techniques such as pharmacological blockade, selective lesions, targeted mutations in conjunction with existing information about individual neurons, will guide quantitative modeling of the ERG. When the components from various cell types have been characterized, models will be developed to describe each of them, and ultimately the models for all components will be combined to provide a complete ERG model in both species. The existence of such models for the normal ERG should greatly aid in the analysis of recordings from normal and diseased eyes.
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