The goal of this project is to understand the generation and transmission of electrical signals in the neurons of the retina. Two different approaches to this goal will be pursued. First, the mechanisms of neurotransmitter release from synaptic terminals of tineal neurons will be studies. this is a fundamental aspect of all neuronal communication. Chemical neurotransmitter is released from synaptic terminals via calcium triggered exocytosis of synaptic vesicles, and this fundamental process will be studied by monitoring the changes in membrane surface area accompanying vesicle fusion in single synaptic terminals. In addition, the mechanisms of membrane retrieval (endocytosis) after vesicle fusion will also be examined. Because neurotransmitter releasers controlled by presynaptic calcium influx, experiments will also be conducted to determine the mechanisms controlling internal calcium in synaptic terminals, including uptake, extrusion, and buffering mechanisms on the one hand, and calcium entry on the other. Second, voltage-dependent sodium channels of the retina will be examined, from both physiological and molecular biological viewpoints. voltage dependent sodium channels are responsible for the generation of sodium action potential, the ubiquitous long distance electrical signal of the nervous system. In the retina, however, some classes of neuron express voltage dependent sodium channels, while other do not. In addition, there are multiple subtypes of sodium-channel gene, expressed differentially in different parts of the nervous system, including in the retina. Experiments will be conducted to examine the molecular regulation of this differential sodium-channel expression in retinal cells. Transcription factor(s) and the genetic regulatory elements with which they interact will be identified, and the regulation of channel expression by growth factors will also be studied. These two lines of research will provide information about basic aspects of retinal signal processing and about genetic mechanisms that control neuronal phenotype in the retina. The results will also be of general significance for neuronal function in other parts of the nervous system outside the retina.
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