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Chi Zhang, Regina D. Nobles, Heiko Schmid, Maureen A. McCall; A Shared Role for Glycine Receptor Subunits α2 and α3 in Retinal On- but not Off-Pathway Signaling. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4579.
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© ARVO (1962-2015); The Authors (2016-present)
We have examined visually evoked responses of retinal ganglion cells (RGCs) in two glycine receptor knockout (GlyR KO) mice. One lacks expression of GlyRα2 (Glra2-/-), the other, GlyRα3 (Glra3-/-). We now examine RGC responses in double KO mice (Glra2-/-/a3-/-), where expression of both GlyRα2 and α3 are absent, to determine whether: (1) the specific receptors mediate distinct inhibitory inputs to RGCs and (2) changes RGC responses in single KOs are consistent with the absence of only that GlyR subunit.
Visually-evoked extracellular responses were recorded from ON and OFF RGC axons in vivo. RF organization was defined using spots of standing contrast whose outer diameter varied (4.2-52°). Bright (100cd/m2) or dark (3cd/m2) spots, presented on the same background (20cd/m2), stimulated ON or OFF RGCs, respectively. Responses were analyzed and RF excitatory center properties compared between the two single and the double KOs. Fixed retinas were cryosectioned and immunohistochemistry with various antibodies labeled specific cell types and receptors. Confocal microscopy was used to acquire images.
In ON double KO RGCs, the transient (peak firing) and sustained (maintained firing) components of the RF center response are reduced compared to single KO ON RGCs. In OFF double KO RGCs, these RF center response components tend to be lower compared to single KO OFF RGCs, but the differences are not statistically significant. Retinal morphology is similar across genotype.
Reduction of both transient and sustained RF center response components in Glra2-/-/a3-/- ON RGCs compared to single KOs suggests an additive GlyRα2 and GlyRα3 disinhibition in the WT On circuit. Because these differences are not observed in Glra2-/-/a3-/- OFF RGCs, it is probably that these inhibitory inputs act independently in the WT Off pathway. The direction and type of differences between single and double KO RGCs support the idea that the changes we detect result only from the absence of the targeted receptor, and not secondary to other alternations.
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