The role of GABACR-mediated inhibition in the parallel rod/cone and on/off retinal pathways

Inhibition is critical in shaping spatial and temporal aspects of visual responses of retinal ganglion cells (RGCs). The GABAc receptor (GABAcR) provides feedback inhibition at bipolar cell terminal in the inner plexiform layer (Lukasiewicz et al., 2004). The expression of GABAcRs at the axon terminals of rod bipolar cells (RBCs) and in shaping their inhibitory currents is well known (Fletcher et al., 1998; Eggers and Lukasiewicz, 2006 a&b). RBCs have a higher proportion of GABA cR mediated current than the cone bipolar cells (McCall et al., 2004; Eggers et al., 2007). To study the role of GABAcR-mediated inhibition in visual processing a knockout mouse (GABAcR Null mouse) was created. Initial studies demonstrated that retinal expression of GABAcRs is absent and that there is no compensatory upregulation of other inhibitory mechanisms (McCall et al., 2002; Lukasiewicz et all, 2004; Sagdullaev et al., 2006; Eggers and Lukasiewicz, 2006). Most previous experiments have focused on the changes in GABA currents at the bipolar cell level and on changes in the responses of cone pathway driven RGCs. I extended these studies by examining how GABAcR-mediated inhibition shapes the receptive field center and surround response properties of RGCs when their input arises via the cone and rod pathways and compared differences between the pathways. I found that GABAcR-mediated inhibition shapes the spontaneous activity of cone and rod pathway driven ON- and OFF-center RGCs. It also contributes to RGCs decreased firing rate at the offset of an excitatory stimulus in cone pathway driven OFF-center RGCs and rod pathway driven ON- and OFF-center RGCs. When RGCs are cone pathway driven, GABAcR-mediated inhibition shapes their responses in a contrast dependent fashion. The RF surround of cone pathway driven ON- and OFF-center RGCs is generated, in part, by GABA cR-mediated inhibition. Finally, GABAcR-mediated inhibition generates most of the RF surround in rod pathway driven ON-center RGCs. My findings support the notion that the initial concept of an RF center with a single antagonistic surround appears to be giving way to a more complex concept of multiple surround mechanisms that are mediated by different inhibitory receptors under different stimulus conditions.