The steeper I-V relation observed in the absence of the GABAergic input should reduce the dynamic range of the ERG b-wave light responses in D1R−/− and GABACR−/− mice. Indeed, the rod-driven b-wave stimulus-response curves, both in the dark and at each background light intensity, obtained from both D1R−/− and GABACR−/− mice displayed a systematic ∼2-fold decrease in their dynamic range, defined as the range of intensities covering between 5% and

95% of the maximal response ( Figure 6), which served as a reason for decreased overall operational range, as illustrated click here in Figures 1C, 2B, and 2D. Altogether, our results argue that GABACRs buy Everolimus mediate a tonic, sensitizing chloride current that hyperpolarizes WT rod DBCs and decreases their input resistance, thereby extending the amplitude and operational range of their depolarizing light responses. In

the final set of experiments, we aimed to identify the cellular source of the dopamine-dependent GABAergic input onto rod DBCs. Electrophysiological studies have described the most prevalent GABACR-mediated chloride currents in rod DBC axon terminals (e.g., Eggers and Lukasiewicz, 2006). However, their dendrites also display a distinct GABACR-mediated chloride conductance, documented in ferret (Shields et al., 2000), which is consistent with specific GABACR immunostaining of rod DBC dendrites and its absence in GABACR−/− rod DBCs ( McCall et al., 2002). Figure 7 shows that short GABA puffs evoked GABACR-mediated chloride currents in both the axonal and dendritic terminals of the same WT rod DBCs in the mouse. Complete suppression of GABA-dependent currents could only be achieved by blocking both GABAA and GABAC receptors. Interestingly, the relative Rolziracetam contributions of GABAAR- and GABACR-dependent currents were similar for dendrites and axon terminals ( Figures 7C and 7D). The latter finding is consistent with results obtained for rat ( Euler and Wässle, 1998)

and for mouse ( McCall et al., 2002) rod DBC axon terminals. Therefore, both axons and dendrites could be considered as potential sites of sustained GABAergic inputs. Furthermore, both axons and dendrites of rod DBCs are located postsynaptically to cells displaying strong immunostaining for D1R and GABA (amacrine and horizontal cells, respectively; Figure 1D and Figure S4). The expression pattern of KCC2 on both rod DBC axons and somas immediately adjacent to the relatively short dendrites (Figures 4C and 4D) predicts an efficient chloride extrusion over the whole length of the rod DBC and therefore does not favor either amacrine or horizontal cells as a major source of the GABAergic input.