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Kathryn M. Heath, Stephanie J. Heflin, Maureen A. McCall; Allelic Grm6 Variants Create Different Light-Evoked Murine Retinal Ganglion Cell Responses. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3030.
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© ARVO (1962-2015); The Authors (2016-present)
Three no b-wave (nob) mouse mutants harbor different mutations in the metabotropic glutamate receptor type 6 (mGluR6) gene (Grm6). RGCs in Grm6 mutants characterized using extracellular recordings, show increases in visually non-responsive (NR) RGCs and RGCs with delayed response at light onset (dON)1,2,3. We examined the structure/function relationships of Grm6-/- and Grm6nob3 RGCs to test the hypothesis that these phenotypes arise or are uncovered in the absence of On pathway signaling.
Retinas were dissected under dim red light and whole cell patch clamp recordings were made from RGCs using electrodes filled with intracellular solution containing Lucifer Yellow (LY). Responses to full field light stimuli were recorded. Retinas were incubated with anti-LY 1o and fluorescent 2o antibodies to classify RGCs based on dendritic lamination and morphology using confocal microscopy. Only RGCs with both structure/function data are included.
We found no gross morphological abnormalities in Grm6-/- or Grm6nob3 RGCs. 70% (19/27) of Grm6-/- RGCs are NR. They include all morphological types: all ON (9/9) and Bistratified (8/8) and 20% (2/10) of OFF RGCs. In contrast, only 45% (9/20) of Grm6nob3 RGCs are NR and their morphologies were ON (5/5) and Bistratified (4/6). Among responsive Grm6-/- RGCs, 38% (3/8) are dON and all have OFF morphology. In contrast, none (0/11) of the responsive Grm6nob3 cells are dON, rather they have OFF responses and have either OFF (n=8) or Bistratified (n=3) morphology.
These data are inconsistent with a simple deficit in On pathway signaling in the mutants. NR Grm6-/- RGCs can be any morphological type and Grm6-/- RGCs with OFF morphology can have any response type. While the two mutants have grossly similar phenotypes (ERG, immunohistochemistry) and the RGCs have similar morphology, there are allelic differences. Grm6nob3 RGCs with dON responses and OFF morphology are not found. Our results suggest that changes occur either in signaling through existing and/or development of the retinal circuits.1. Rentería et al. J. Neurosci. 26, 11857-69 (2006)2. Pinto et al. Vis Neurosci. 24, 111-23 (2007)3. Maddox et al. J. Physiol. 586, 4409-24 (2008)
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