Dopamine modulates the off pathway in light-adapted mouse retina

DL-2-Amino-4-phosphonobutyric acid (APB) is often used as a tool to block On pathways in studies of interactions between On and Off pathways in retinas. APB is an agonist of mGluR6 receptors and hyperpolarizes the On cone bipolar cells and rod bipolar cells. How APB affects Off responses of retinal ganglion cells (RGCs) in mouse retinas under dark and light adaptation is not clear. The light-evoked excitatory postsynaptic currents (light-evoked EPSCs) from Off and On-Off RGCs cells were recorded using whole-cell patch-clamp recording to assess how APB affects Off responses (light-evoked Off EPSCs) of RGCs in dark- and light-adapted mouse retinas. We found that APB differentially affected Off responses of RGCs in dark- and light-adapted mouse retinas. Under dark adaptation, while the APB-sensitive Off responses were blocked, APB increased the remaining Off responses (mainly from the secondary rod Off pathways) via removal of inhibition from On pathways to Off pathways. Under light adaptation, APB decreased Off responses. Glycinergic and GABAergic antagonists did not prevent the APB-induced reduction of Off responses of RGCs; however, a dopaminergic type 1 receptor (D(1)) blocker (SCH 23390) and a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker (ZD 7288) prevented the APB-induced reduction of Off responses of RGCs under light adaptation. The results indicated afunctional circuit: On cone bipolar cells to Off cone bipolar cells via D(1) receptors and HCN channels.