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Gordon and Llura Gund Research Professor of Neurosciences

John Dowling

Gordon and Llura Gund Research Professor of Neurosciences

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John Dowling lab

Research

 

The vertebrate retina is an accessible part of the central nervous system; an understanding of retinal mechanisms provides clues concerning neural mechanisms throughout the brain. Over the years, my group has been concerned with the cells of the retina-their structure, function, pharmacology, genetics, and synaptic interactions as well as their functional organization.

I am now a Research Professor and have closed my laboratory. However, I am presently working with Professor Jeff Lichtman and his colleagues, along with two collaborators at the University of Washington in Seattle, to reconstruct the fovea of the human retina. The fovea, a small indented retinal area on the visual axis of the eye, is responsible for all of our high acuity vision. Indeed, reading, recognizing faces, driving and watching television all depend on good foveal vision. If the fovea is damaged, as happens in Age-Related Macular Degeneration, a person loses these abilities, and is termed legally blind, the most common cause of legal-blindness in the western world. Using connectomic methods developed in the Lichtman laboratory, and human tissue obtained by our Seattle colleagues, we are cutting thousands of sections (4000 so far). We have imagined 1500 of them, resulting in the generation of 30,000 images that are being analyzed and reconstructed.

Selected Publications

Dowling, J. E. and Wald, G. Vitamin A deficiency and night blindness. Proc. Natl. Acad. Sci., 44, 648-661, 1958.

Dowling, J. E. and Wald, G. The biological function of vitamin A acid. Proc. Natl. Acad. Sci., 46, 587-608, 1960.

Dowling, J. E. and Sidman, R. L. Inherited retinal dystrophy in the rat. J. Cell Biol., 14, 73-109, 1962.

Dowling, J. E. Neural and photochemical mechanisms of visual adaptation in the rat. J. Gen. Physiol., 46, 1287-1301, 1963.

Dowling, J. E. Synaptic organization of the frog retina: an electron microscopic analysis comparing the retinas of frogs and primates. Proc. Roy. Soc. B, 170, 205-228, 1968.

Miller, R. F. and Dowling, J. E. Intracellular responses of the Müller (glial) cells of mudpuppy retina: their relation to the b-wave of the electroretinogram. J. Neurophysiol., 33, 323-341, 1970.

Chappell, R. L. and Dowling, J. E. Neural organization of the ocellus of the dragonfly. I. Intracellular electrical activity. J. Gen. Physiol., 60, 121-147, 1972.

Dowling, J. E. and Ripps, H. Effect of magnesium on horizontal cell activity in the skate retina. Nature, 242, 101-103, 1973.

Dowling, J. E. and Ehinger, B. Synaptic organization of the amine-containing interplexiform cells of the goldfish and Cebus monkey retinas. Science, 188, 270-273, 1975.

Pepperberg, D., Lurie, M., Brown, P. K. and Dowling, J. E. Visual adaptation: effects of externally applied retinal on the light-adapted, isolated skate retina. Science, 191, 394-396, 1976.

Armett-Kibel, C., Meinertzhagen, I. A. and Dowling, J. E. Cellular and synaptic organization in the lamina of the dragonfly Sympetrum rubicundulum. Proc. Roy. Soc. Lond. B, 196, 385-413, 1977.

Lasater, E. M. and Dowling J. E. Carp horizontal cells in culture respond selectively to L-glutamate and its agonists. Proc. Natl. Acad. Sci., 79, 936-940, 1982.

Lasater, E. M. and Dowling, J. E. Dopamine decreases the conductance of the electrical junctions between cultured retina horizontal cells. Proc. Natl. Acad. Sci 82, 3025-3029, 1985.

Knapp, A. G. and Dowling, J. E. Dopamine enhances excitatory amino acid-gated conductances in cultured retinal horizontal cells. Nature, 325, 437-439, 1987.

Zucker, C. L. and Dowling, J. E. Centrifugal fibers synapse on interplexiform cells in teleost retina. Nature, 330, 166-l68, 1987.

Hyatt, G. A., Schmitt, E. A., Marsh-Armstrong, N., McCaffery, P., Dräger, U. and Dowling, J. E. Retinoic acid establishes ventral retinal characteristics, Development, 122, 195-204, 1996.

Knapp, A. G., Schmidt, K. F. and Dowling, J. E. Dopamine modulates the kinetics of ion channels gated by excitatory amino acids in retinal horizontal cells. Proc. Natl. Acad. Sci., 87, 767-771, 1990.

Hyatt, G. A., Schmitt, E. A., Marsh-Armstrong, N. R. and Dowling, J. E. Retinoic acid-induced duplication of the zebrafish retina, Proc. Natl. Acad. Sci., 89, 8293-8297, 1992.

Qian, H. and Dowling, J.E. Novel GABA responses from rod-driven retinal horizontal cells. Nature, 361, 162-164, 1993.

Marsh-Armstrong, N., McCaffery, P., Gilbert, W., Dowling, J. E. and Dräger, U. C. Retinoic acid is necessary for development of the ventral retina in zebrafish. Proc. Natl. Acad. Sci., 91, 7286-7290, l994.

Brockerhoff, S. E., Hurley, J. B., Janssen-Bienhold, U., Neuhauss, S. C., Driever, W. and Dowling, J. E. A behavioral screen for isolating zebrafish mutants with visual system defects. Proc. Natl. Acad. Sci., 92, 10545-10549, 1995.

Brockerhoff, S. E., Hurley, J. B., Niemi, G. A. and Dowling, J. E. A new form of inherited red-blindness in zebrafish. J. Neurosci., 17, 4236-4242, 1997.

Fadool, J. M., Hartl, D. L. and Dowling, J. E. Transposition of the mariner element Drosophila mauritiana in zebrafish. Proc. Natl. Acad. Sci., 95, 5182-5186, 1998.

Darland, T. and Dowling, J. E. Behavioral screening for cocaine sensitivity in mutagenized zebrafish. Proc. Natl. Acad. Sci., 98, 11691-11696, 2001.

Emran, F. Rihel, J., Adolph, A., Wong, K. Y., Kraves, S. and Dowling, J. E. OFF- ganglion cells cannot drive the optokinetic reflex in zebrafish. Proc. Natl. Acad. Sci., 104, 19126-19131, 2007.

Leung, Y. F., P. Ma, Link, B. A. and Dowling, J. E. Factorial microarray analysis of zebrafish retinal development, Proc. Natl. Acad. Sci., 105, 12909-12914, 2008.

Emran, F., Rihel, J. Adolph, A.A. and Dowling, J. E. Larval zebrafish lose vision at night.   Proc. Natl. Acad. Sci. 107, 6034-6039, 2010.