STRUCTURAL NEUROCHEMISTRY OF RETINAL CIRCUITS

University Of Utah, Salt Lake City UT

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Abstract

DESCRIPTION (Applicant's Description): The long-term goals of this research are to phenotype the metabolic chemistries of all retinal cells and define the retinal signaling properties critical for the development of artificial vision systems. Specific Aim 1. Generation of a metabolic phenotype atlas for the mammalian retina. Metabolic phenotypes of all retinal cells will be extracted with metabolite probes and formal classification analysis. Significance: Metabolic phenotypes uniquely capture the normal biochemistry of the mammalian retina with single-cell resolution, which is essential and prefatory to quantitative screening of disease states and genetic models. Specific Aim 2. Characterization of the ionotropic glutamatergic drive for all retinal neurons. Functional drive mediated by ionotropic glutamate receptors will be defined for all neurons via excitation and signature mapping with channel-permeant probes. Significance: Visual sensitivities are powerfully shaped by ionotropic glutamate receptors. Excitation mapping uniquely exposes functional receptor expression with single-cell resolution and permits global screening of novel neuroactive and neuroprotective drugs. Specific Aim 3. Mapping the synaptic patterns of cone bipolar cell -> target cell complexes. Combined signature, excitation and overlay mapping will simultaneously detail glutamate-gated drive and novel nested feedback-feedforward circuits that shape ganglion cell function. Significance: Current retinal models fail to capture the true circuit designs of the retina, including circuits with new and unexpected features that may be pivotal in crafting useful artificial vision systems.