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Leah Jean Middleton, Ralph F Nelson; Plastic changes in ganglion cell spectral responses after transgenic manipulation of the zebrafish cone mosaic.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2599.
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© ARVO (1962-2015); The Authors (2016-present)
The tetrachromatic (red, green, blue and UV cone) zebrafish overproduces red cones at the expense of other types upon transgenic miss-expression of the thyroxin β2 nuclear receptor (trβ2) in all photoreceptor progenitors (Suzuki et al., 2013). We examine the impact of this perturbation on retinal circuits for wavelength discrimination seen in retinal ganglion cells (rGCs).
The spectral sensitivities of rGCs were recorded in both wildtype (WT) and crx:trβ2 larvae at 5, 6, 7, and 11 or 12 dpf. Eyes were removed, inverted to expose the optic nerve, stabilized with a droplet of agarose, and perfused with oxygenated MEM while a microelectrode (with 500µM NaCl) was inserted into the optic nerve to record single-fiber spike responses. Eyes were exposed to 280 spectral stimuli covering 9 wavelengths (330-650nm). Spectra were fit by a ‘sum of Hill functions’ model. Responses of 44 WT and 55 crx:trβ2 rGCs were categorized by temporal and spectral properties. The distribution of rGCs across these categories was compared between WT and crx:trβ2 fish using a chi-squared test.
ON rGCs were less frequent (p = 0.05) in crx:trβ2 as compared to WT, but ON-OFF rGCs were more frequent (p < 0.0001). Light offset responses of crx:trβ2 ON-OFF and OFF cells more frequently responded to red cones (p < 0.05), but were less frequently responsive to green (p < 0.05), blue (p < 0.05), and UV (p < 0.001) inputs. A greater proportion of light offset components were driven solely by red cone inputs (p < 0.05). Interestingly, at light onset, the frequency of rGCs excited or inhibited by green (p = 0.255), blue (p = 0.987), or UV cones (p = 0.228) did not differ. In crx:trβ2 rGCs, a greater proportion of cells were inhibited at stimulus onset by red cones (p < 0.001), but a similar proportion were excited at light onset by red cones (p = 0.082).
Despite reduced density of green, blue, and UV cones in crx:trβ2, at light onset, rGCs were just as frequently excited or inhibited by these pathways, suggesting a circuitry compensation. The greater proportion of onset responses with red-cone inhibition suggests circuitry reorganization, as does the greater frequency of light offset responses to red cones, many of which are driven solely by red cones. The more robust OFF-pathway in crx:trβ2’s results in a greater proportion of ON-OFF rGCs.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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