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R. D. Nobles, C. L. Cepko, U. Muller, H. Betz, M. A. McCall; Glycine Receptor Subunits -3 and -2 Differentially Contribute to the RF Organization of OFF-Center Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3857. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Glycine and GABA are the primary inhibitory neurotransmitters in the retina. Different glycine receptor (GlyR) subunits have been localized within the retina, but a lack of specific subunit antagonists has limited the analysis of their functional contribution to retinal signaling. To define the role of these subunits in the receptive field (RF) organization of RGCs, we compared visually-evoked responses of ON- and OFF-center retinal ganglion cells (ON and OFF RGCs) from knock-out (KO) mice for GlyR subunits α2 (Glra2-/-) and α3 (Glra3-/-) to those of C57Bl/6J (WT) mice.
Visually-evoked activity was recorded from RGC axons, using an anesthetized, in vivo, extracellular preparation. RF properties of Glra2-/-Glra3-/- and WT OFF RGCs were assessed using spots of varying diameter and contrast (within the linear response range). Under light adapted (LA) conditions (20cd/m2 background), dark spots (0 or 3cd/m2) were centered on the cell’s RF evoked responses. Under dark adapted (DA) conditions (0cd/m2 background), bright spots (3cd/m2) were used. Peak responses and maximum antagonism in RGCs from each line were determined.
Under LA conditions, the peak responses to high contrast spots in Glra3-/- OFF RGCs were greater than either Glra2-/- or WT, which were similar. The RF center diameter was also smaller in Glra3-/- OFF RGCs than the other two lines. At DA levels, the RF center diameter was smaller in both Glra3-/- and Glra2-/- OFF RGCs compared to WT. This decrease is caused, in part, by an increase in the influence of the RF surround. The RF organization of ON RGCs in both GlyR KOs did not differ from WT.
GlyRα3 and GlyRα2 mediated inputs are important for RF center/surround organization in OFF, but not ON RGCs. This is consistent with the localization of GlyRα3 and GlyRα2s in the OFF strata of the inner plexiform layer. The differences in Glra3-/- and Glra2-/- OFF RGC responses suggest they participate in different retinal circuits. Specifically, GlyRα3-mediated inhibition contributes to RF center response tuning as a function of contrast and adaptation level. The similarity in the increase in maximum antagonism in Glra3-/- and Glra2-/- OFF RGCs suggests that both act to decrease inhibitory drive to WT OFF RGC surrounds.
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