ZFIN ID: ZDB-LAB-170512-1
Ralph Nelson Lab
PI/Director: Nelson, Ralph
Contact Person: Nelson, Ralph
Email: nelsonr@ninds.nih.gov
URL: https://neuroscience.nih.gov/ninds/Faculty/Profile/ralph-nelson.aspx
Address: 5625 Fisher’s Lane Room 4S26E Rockville MD 20852
Phone: 301-496-8133
Fax: 3012-594-2276
Line Designation: nds

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NIH targeted zebrafish as a model system for the study of human genetic disease. The PI’s research program develops zebrafish as a model of visual system function, with focus on retinal processing of wavelength/color information. In vertebrates, retinal neural circuits process images, extracting information about color, shape, size and movement from visual surroundings. While laboratory mammals such as cat, rat, mouse and rabbit have provided outstanding models of nocturnal vision, zebrafish is remarkable for its diurnal color vision. Zebrafish is a tetrachromat with 4 cone photoreceptor types that select from among 8 opsin genes (1) to provide separate channels for red, green, blue and ultraviolet wavebands. In addition to the wavelength range visible to primates, zebrafish perceive extra colors within the near UV.

The PI’s recent work employed microelectrodes to sample individual neural responses to different wavelengths, as photic signals pass through sequential stages within retinal neural layers. In distal retina, horizontal cells, which are in direct communication with cones, subtract signals arising from cones with different opsins (2). In proximal retina, the spectral signatures of amacrine cell morphological types are unique (3). Both horizontal cells and amacrine cells are interneurons, modifying visual signals as they pass from cone cells to ganglion cells, and ultimately to brain visual areas through the optic nerve. In the present progress report and proposal, genetic manipulations of cone development change the pattern of signals that retinal horizontal, bipolar, amacrine and ganglion cells must process. The physiological penetrance of these genetic manipulations is first characterized in spectral shapes of electroretinographic (ERG) signals isolated from cone populations. Later stages of this research study circuitry adaptation in single unit responses after manipulation of the cone mosaic.

Middleton, Leah Graduate Student

Guo, C., Deveau, C., Zhang, C., Nelson, R., Wei, X. (2020) Zebrafish Crb1, localizing uniquely to the cell membranes around cone photoreceptor axonemes, alleviates light damage to photoreceptors and modulates cones' light responsiveness. The Journal of neuroscience : the official journal of the Society for Neuroscience. 40(37):7065-7079
Deveau, C., Jiao, X., Suzuki, S.C., Krishnakumar, A., Yoshimatsu, T., Hejtmancik, J.F., Nelson, R.F. (2020) Thyroid hormone receptor beta mutations alter photoreceptor development and function in Danio rerio (zebrafish). PLoS Genetics. 16:e1008869
Nelson, R.F., Balraj, A., Suresh, T., Torvund, M., Patterson, S.S. (2019) Strain variations in cone wavelength peaks in situ during zebrafish development. Visual neuroscience. 36:E010
Li, L., Jiao, X., D'Atri, I., Ono, F., Nelson, R., Chan, C.C., Nakaya, N., Ma, Z., Ma, Y., Cai, X., Zhang, L., Lin, S., Hameed, A., Chioza, B.A., Hardy, H., Arno, G., Hull, S., Khan, M.I., Fasham, J., Harlalka, G.V., Michaelides, M., Moore, A.T., Coban Akdemir, Z.H., Jhangiani, S., Lupski, J.R., Cremers, F.P.M., Qamar, R., Salman, A., Chilton, J., Self, J., Ayyagari, R., Kabir, F., Naeem, M.A., Ali, M., Akram, J., Sieving, P.A., Riazuddin, S., Baple, E.L., Riazuddin, S.A., Crosby, A.H., Hejtmancik, J.F. (2018) Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa. PLoS Genetics. 14:e1007504
Tanvir, Z., Nelson, R.F., DeCicco-Skinner, K., Connaughton, V.P. (2018) One month of hyperglycemia alters spectral responses of the zebrafish photopic ERG. Disease models & mechanisms. 11(10):