Lab
Ralph Nelson Lab
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Statement of Research Interest
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.
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.
Lab Members
| Middleton, Leah Graduate Student |