Glycine receptor subunits -a2 and a3 participate in different inhibitory circuits that alter the receptive field organization of on- and off-center retinal ganglion cells.

Abstract

In the retina, the receptive fields (RFs) of most neurons are comprised of an excitatory center and a suppressive surround. Retinal ganglion cell (RGC) RF center excitatory input arises from bipolar cell (BC) inputs, while their surround arises from lateral inhibitory inputs. Because of the availability of selective antagonists the role of GABAergic inputs has been well defined. In contrast, the role of individual glycine receptor (GlyR) subunit inhibition is less clear because the antagonist, strychnine, blocks all GlyR subunit combinations. To define individual retinal circuits that utilize specific glycinergic subunits, I examined maintained and visually-evoked responses of ON- and OFF-center GCs from mice lacking expression of the GlyRa2 (Glra2-/-) or GlyRa3 (Glra3-/-) subunits to those of C57Bl/6J (WT) RGCs using an in vivo extracellular approach. Previous observations have defined glycine and GABA inputs across BC classes and in a variety of amacrine and RGCs. Using this information and by comparing the responses of WT vs. Glra2-/- and Glra3-/- RGCs; I conclude that both subunits modulate local RF interactions. Within the On pathway, GlyRa2 and GlyRa3 inputs play similar roles. Their responses predict that they participate in serial inhibitory circuits that decrease a direct GABAergic inhibition that modulates maintained, but not peak firing rates. In contrast within the Off pathway, GlyRa2 and GlyRa3 inputs define two populations of RGCs. In one, GlyRa2 participates in a serial inhibitory circuit that modulates maintained firing, whereas in the other, GlyRa,3 mediates direct inhibition that controls the peak firing rate. Only GlyRa2 modulates lateral interactions to the RF surround where it mediates a direct inhibitory input to all OFF-center RGCs. My results suggest that GlyRa2 and GlyRa3 inputs define two populations of OFF-center RGCs. In addition, both subunits participate in retinal circuits that can be distinguished not only by the RGC RF center type, but also by the type of inhibitory circuit. These results are the first demonstration of subunit specific control of RGC visual responses and, are the first evidence of serial glycine to GABA as well as glycine to glycine circuits in the retina