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D. R. Cantrell, S. Inayat, L. H. Pinto, J. B. Troy; Characterization of nob4 Retinal Ganglion Cell (RGC) Responses to Visual Stimulation. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4601.
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© ARVO (1962-2015); The Authors (2016-present)
The nob4 mutant mouse was found by electroretinographic (ERG) screening of a population of C57BL/6J mice that had been subjected to genome-wide mutagenesis with N-ethyl-N-Nitrosourea. ERGs of the nob4 retina lack the b-wave indicating a dysfunction of the ON-pathway. This mutation causes a substitution of Pro for Ser at position 185 in the mGluR6 receptor, which is located in wild type (WT) mice at the post-synaptic terminal of ON-Bipolar cells. The mutation in this receptor and the lack of the b-wave predict the loss of RGC ON responses in the nob4 retina. The purpose of this project was to characterize quantitatively the ON and OFF responses of nob4 mice.
RGC responses were recorded from isolated WT and nob4 retinas (post natal day 21-35) using a multi-electrode array (Muti Channel Systems Gmbh, Germany). The visual stimulus consisted of a 1s light ON period (luminance of 2 cd/m2 cast onto the retina) alternated with a 1s light OFF period. Spikes were detected from the filtered voltage signals recorded by the electrodes and sorted to identify individual cells using principal component analysis of the spike waveforms (Offline Sorter, Plexon Inc.). Peristimulus time histograms (PSTHs) were generated for each cell and the cells classified as ON, OFF, ON-OFF, OTHER or NON-RESPONSIVE. Response latency and the time course of high spike activity were also analyzed.
The RGC population in WT retina (163 cells) consisted of 21% ON, 15% OFF, 44% ON-OFF, 6% OTHER and 14% NON-RESPONSIVE cells. The RGC population in the nob4 retina (153 cells) consisted of 1% ON, 26% OFF, 50% ON-OFF, 9% OTHER, and 14% NON-RESPONSIVE. The average latency of the ON response of the nob4 ON-OFF cells (0.64 ± 0.30 [s.d.] secs) was much greater than the latency observed in WT (0.15 ±0.10 [s.d.] secs).
Compared to WT, the proportion of ON cells in nob4 retina is greatly reduced, and the ON response of nob4 ON-OFF cells greatly delayed. In conclusion, the nob4 RGC population demonstrates a severely compromised ON-response. The nob4 mutant is therefore an excellent animal model in which to study contributions of ON signals to vision.
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