The goal of this project is to understand how electrical signals are generated and processed in the neurons of the retina. The approach to this goal is to study ionic conductances of single, isolated neurons and to determine how those conductances are modulated by neurotransmitters. Then, the information obtained from these studies of single neurons will be used to make testable predictions about the effects of transmitters on light responses in intact retina. In that way, fundamental information can be obtained about how the neural circuitry of the retina extracts information about the visual world. A particular focus of the work will be the regulation of intracellular calcium in individual synaptic terminals of retinal neurons. The intracellular calcium concentration controls the release of chemical transmitter from neurons, and thus factors that regulate internal calcium will be important in modulating synaptic transmission. These factors include neurotransmitters released by other neurons, which can either potentiate or inhibit the calcium channels through which external calcium can enter the synaptic terminal. To study this neurotransmitter modulation of calcium channels, combined electrical measurements of ionic current and fluorescent-indicator measurements of internal calcium concentration will be made simultaneously in single synaptic terminals of retinal neurons. The resulting information will be valuable not only in understanding the retina, but also the rest of the central nervous system, where modulation of presynaptic calcium current is thought to be an important mechanism by which neurotransmitters modulate synaptic transmission.
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