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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National Eye Institute (NEI)
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Visual Sciences A Study Section (VISA)
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Harvard University
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Wasfy, Meagan M; Matsui, Jonathan I; Miller, Jessica et al. (2014) myosin 7aa(-/-) mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses. Exp Eye Res 122:65-76
Fadool, James M; Dowling, John E (2008) Zebrafish: a model system for the study of eye genetics. Prog Retin Eye Res 27:89-110
Wong, Kwoon Y; Dowling, John E (2005) Retinal bipolar cell input mechanisms in giant danio. III. ON-OFF bipolar cells and their color-opponent mechanisms. J Neurophysiol 94:265-72
Wong, Kwoon Y; Cohen, Ethan D; Dowling, John E (2005) Retinal bipolar cell input mechanisms in giant danio. II. Patch-clamp analysis of on bipolar cells. J Neurophysiol 93:94-107
Kainz, Pamela M; Adolph, Alan R; Wong, Kwoon Y et al. (2003) Lazy eyes zebrafish mutation affects Muller glial cells, compromising photoreceptor function and causing partial blindness. J Comp Neurol 463:265-80
Mangrum, Wells I; Dowling, John E; Cohen, Ethan D (2002) A morphological classification of ganglion cells in the zebrafish retina. Vis Neurosci 19:767-79
Allwardt, B A; Lall, A B; Brockerhoff, S E et al. (2001) Synapse formation is arrested in retinal photoreceptors of the zebrafish nrc mutant. J Neurosci 21:2330-42
Li, L; Dowling, J E (2000) Disruption of the olfactoretinal centrifugal pathway may relate to the visual system defect in night blindness b mutant zebrafish. J Neurosci 20:1883-92
Li, L; Dowling, J E (2000) Effects of dopamine depletion on visual sensitivity of zebrafish. J Neurosci 20:1893-903
Link, B A; Fadool, J M; Malicki, J et al. (2000) The zebrafish young mutation acts non-cell-autonomously to uncouple differentiation from specification for all retinal cells. Development 127:2177-88

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