International Research Fellowship Program: Functional Analysis of Electrical Feedback from Horizontal Cells to Cone Photoreceptors

Shields, Colleen, St. Louis MO

Investigators

Abstract

0202703 Shields The International Research Fellowship Program enables U.S. scientists and engineers to conduct three to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad. This award will support a twenty-four month research fellowship by Dr. Colleen Shields to work with Dr. Maarten Kamermans at the Netherlands Ophthalmic Research Institute in Amsterdam, Netherlands. This project aims at a functional characterization of the network formed by the cones, horizontal cells, and bipolar cells in the vertebrate retina. The negative feedback pathway from horizontal cells to cones is an essential element of this network. Although we are approaching a quantitative description of this first stage of retinal processing, no psychophysical correlate for this network activity exists. Fortunately, a new tool for analysis of horizontal cell function from the cellular to the behavioral levels has recently become available. Recent studies in the Kamermans laboratory have indentified connexin 26 (Cx26) hemichannels as key actors in the communication between horizontal cells and cones. Cx26 forms putative hemichannels on horizontal cell dendrites near the glutamate release site of the cones. Blocking these hemichannels abolishes all feedback-mediated responses in cones and horizontal cells, suggesting an ephaptic feedback mechanism in which the release of neurotransmitter by the cones depends on the polarization of the horizontal cells. To do this, they will generate transgenic zebrafish with a modified dominant negative Cx26. Wild type and transgenically modified animals will be studied electrophysiologically to verify the importance of Cx26 hemichannels in the feedback from horizontal cells to individual cone photoreceptors. The creation and study of zebrafish lacking Cx26 function will yield a quantitative physiological description of this neural network and will provide a psychophysical correlate of its role in visual perception in both man and fish. The lab of Dr. Kamermans first described the role of Cx26 in horizontal cell feedback to cones. The expertise in the group encompasses electrophysiology, anatomy, psychophysics, and molecular biology. Dr. Kamermans is an expert in outer retinal circuitry.