This project is attempting to learn more about retinal synaptic mechanisms. In particular, we are seeking to discover what substances are used at specific synaptic junctions and what effects these substances have on retinal cells. It is now generally believed that two basic types of substances are released at brain synapses; neurotransmitters which initiate fast excitatory and inhibitory responses in neural cells, and neuromodulators which mediate slow, long lasting events in nerve cells. The next five years of this project will focus on the action of, and interaction between, glutamate, a classic neurotransmitter,and dopamine, a classic neuromodulator, on bipolar, amacrine and ganglion cells of the fish (white perch retina). We also will study the pharmacology and molecular biology of a newly identified GABA receptor/channel, the GABA-c receptor, from white perch or hybrid bass retinas. Finally, recordings will be made from cone photoreceptors of zebrafish that absorb maximally in the ultraviolet region of the spectrum. Specific projects planned for the next five years include: 1) A study of amino acid-gated channels in retinal bipolar, amacrine and ganglion cells and their modulation by dopamine and other neuroactive substances. This project is focusing initially on the glutamate-mediated responses of bipolar cells. Bipolar cells in retinal slices are voltage- clamped with patch electrodes and the glutamate responses characterized. 2) A study of the pharmacological and molecular biological properties of GABA-c receptors in retinal horizontal cells and in Xenopus oocytes. This project will examine the conformation of GABA that best activates these novel receptors. This part of the project will employ conformationally- restricted GABA analogues and isolated rod (H4) horizontal cells from the white perch or hybrid bass retinas. Other studies will involve expressing in Xenopus oocytes the gene(s) encoding the subunits that make up these novel receptors. 3) An investigation of the response properties of ultraviolet-sensitive photoreceptors. This project will explore the response properties of UV- sensitive cones isolated from the zebrafish. Suction electrodes will record the currents generated by these photoreceptors.
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