STRUCTURAL NEUROCHEMISTRY OF RETINAL CIRCUITS

University Of Utah, Salt Lake City UT

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Abstract

The long range objectives of this work are to elucidate homeostatic signatures for all cells of the normal retina, explore the dynamics of these signatures under both physiological and pathophysiological challenge and use such signatures to map excitatory networks of the vertebrate retina. We believe this program to be of significance for (1) understanding the details of organization which all artificial vision systems must likely mimic and (2) managing the retinal microenvironment when homeostatic control of pivotal molecular constituents is compromised by trauma, environmental insults, or genetic/acquired disease. Model systems: goldfish, rabbit. Specific Aim 1 is a comprehensive characterization of the amino acid/metabolite signatures for all cells of the vertebrate retina by pattern recognition of the natural amino acids, special amino acids and key carboxylic acids. It will be achieved through immunochemical mapping of serial ultrathin (40 nm) optical microscopic images, image registration and N-dimensional pattern recognition. Specific Aim 2 is a program to define signature responses of all vertebrate retinal cells to photic adaptation, neurochemical drive, hypoxia/hypoglycemia, osmotic challenge. Regulation by dopamine or NO, neurochemical activation through APMA/kainate- or NMDA-gated paths, impacts of hypoxia and hypoglycemia and osmotic challenges will be investigated in vitro and analyzed by both pattern recognition techniques and laminar profiling of the inner plexiform layer. Specific Aim 3 extends the analysis of retinal circuitry by mapping the retinal flow of excitatory signals gated by extracellular glutamate/ACh and intracellular cGMP through non-selective cation channels. Excitation events will be detected with IgGs against channel-permeating cations and mapped into retinal populations with single-cell resolution. Specific Aim 4 is the completion of a comprehensive catalogue of cyprinid retinal neurons using signature techniques superimposed upon both Golgi impregnation and ultrastructural imagery. This catalogue will assign not only a primary neurotransmitter but also a comprehensive signature to a specific morphology and synaptology.