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, L-glutamate, a classic neurotransmitter and dopamine' a classic neuromodulator, on horizontal cells of the fish (white perch) retina. In addition, we will study the modification of electrical junctions between horizontal cells by dopamine, factors underlying the release of dopamine in the retina' &nd finally, the effects of dopamine on retina bipolar, amacrine and ganglion cells. Specific projects planned for the next five years include: 1) The role of phosphorylation in the modulation of glutamate- mediated conductances in horizontal cells by dopamine and cyclic AMP. 2) The nature of single glutamate channels in horizontal cells and their modulation by dopamine and cyclic AMP. 3) The nature of single gap junctional channels between horizontal cells and their modulation by dopamine, cyclic AMP and phosphorylation. 4) The development of synapses between neurons in culture. 5) The effects of neuroactive substances and optic nerve stimulation on dopamine release in the retina. 6) The effects of dopamine on extracellularly recorded ganglion cells and intracellularly recorded bipolar and amacrine cells of the retina.
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