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Ian Scot Pyle, Chi Zhang, Maureen A McCall; Distinct Glycine Receptor Subunit Composition Across Retinal Ganglion Cell Types. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2581. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Glycine inhibition shapes retinal signaling. Glycine receptors (GlyRs) are composed of the same β subunit and one of four α subunits. GlyRα subunits (GlyRαs) are differentially expressed in the inner retina and produce spontaneous inhibitory postsynaptic currents (sIPSCs) with distinct decay kinetics. These factors lead us to hypothesize that feedforward inhibition via specific GlyRαs will differentially modulate ganglion cell (GC) output. As a crucial step to addressing our hypothesis, we characterized expression of GlyRαs across 7 identified GCs.
Using mouse reporter lines (PVCre, TRHR, and W3), we recorded sIPSCs from fluorescently labeled GCs. Glycinergic sIPSCs were isolated in the presence of picrotoxin (PTX; 20μM) and confirmed in both PTX and strychnine (10μM). sIPSC frequency (over 100s) and τdecay of individual glycinergic sIPSCs were measured in WT GCs and used to devise hypotheses about GlyRαs expression. We compared sIPSC frequency (ANOVA) and τdecay (K-S test) in WT GCs with GCs from Glra2, 3 or 4 knockout (KO) mice or after Glra1 knockdown (KD) by injection of a retrogradely transported AAV-Glra1 shRNA construct into the LGN.
Glycinergic sIPSC frequency and τdecay are similar across WT OFFα and ONα, ONT and OFFδ GCs (X=26.5/s; 2.9ms, respectively), consistent with GlyRα1 expression. Glra1 KD eliminates glycinergic sIPSCs in these GCs. WT ON/OFF DS (ooDS) GC glycinergic sIPSC frequency is 5.7/s and τdecay is 21.6ms, consistent with expression GlyRα2 or α4. Although glycinergic sIPSCs frequency is unaltered in Glra2KO or Glra4KO ooDS GCs compared to WT, sIPSCs are eliminated in Glra2KO/Glra4KO ooDS GCs. WT mini-JAMB GC glycinergic sIPSC frequency is 14.1/s and τdecay is 6.5ms, consistent with GlyRα3 expression. sIPSC frequency drops significantly in both Glra2KO and Glra3KO GCs and sIPSCs are eliminated in Glra2KO/Glra3KO mini-JAMB GCs. WT local edge detector (LED) GC glycinergic sIPSC frequency is 14.3/s and τdecay is 7.5ms, consistent with GlyRα3 expression. sIPSC frequency drops significantly in both Glra3KO and Glra1KD GCs.
The 4 mouse GCs with the largest somas express only GlyRα1. Surprisingly, other GCs express GlyRαs with 2 distinct α subunit composition: ooDS GCs express GlyRα2 and α4, mini-JAMB’s express GlyRα2 and α3 and LEDs express GlyRα1 and α3. These results serve as the basis for defining the role of specific GlyRαs in feedforward inhibition to GCs.
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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