The overriding objective of this research is to understand the role of zinc as a neuromodulator. This research project will determine the extent to which zinc contributes to the modulation of photoreceptor transmitter release. Release of transmitter is the important first step in transferring information from the cells which detect light to other neurons that process this information into a visual image via the retina and brain. Moreover, transmitter release is likely to play a role in visual sensitivity and adaptation in normal visual function and disease. Determining the role of zinc in the nervous system remains a major unresolved question in neuroscience today. Reactive zinc (Zn2+ or "ionic" zinc) is co-localized with glutamate in a subset of excitatory neurons, and its release has been demonstrated. Other research suggests that zinc is involved in mechanisms of learning and memory. Dietary zinc supplementation is prescribed clinically for a disease affecting the aging retina, while benefits of reactive zinc removal have been reported in studies concerning mental loss in the aging brain. Thus this research project may have broadly important scientific impacts. One specific objective of this study is to determine the extent to which hemichannel current zinc sensitivity contributes to the enhancement of the electroretinogram (ERG) b-wave observed in the presence of histidine, which removes reactive zinc from the space outside of retinal cells. Hemichannels are the building blocks of gap junctions formed in neuronal membranes. Finding an effect of hemichannel blockers on the enhancement observed in the electroretinogram of the skate (Raja erinacea), where this enhancement was first reported, will support the hypothesis that zinc modulation of a hemichannel feedback pathway is involved. Another objective is to measure the sensitivity of photoreceptor calcium channel currents to zinc while their outer segments are isolated inside suction electrodes. Determining the effects of zinc on this calcium current will support the hypothesis that zinc autofeedback regulation of calcium entry is involved in the histidine-induced ERG enhancement. It is also an objective of the study to examine the physiological consequences of these mechanisms by determining the effects of zinc removal by chelation on the light response of horizontal cells in an intact retina. As second-order retinal neurons, the light response and resting potential of horizontal cells monitor changes in the amounts of photoreceptor transmitter released so that effects of zinc removal and the blocking of hemichannels can be examined directly for evidence of their contributions to feedback. Broader impacts include promotion of teaching, training and learning in an academic research and teaching environment at a college offering scientific educational opportunities to a sizeable minority population. In a department known for its outreach to underrepresented groups and expanding vigorously into the area of molecular neuroscience, the laboratory conducting this study provides a resource for application of basic electrophysiological techniques. Potential benefits to society at large include greater understanding of the role of zinc in vision and disease.
