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In the retina, the ON-and OFF-signals are processed in parallel.Although the signal processing pathway is distinct, the signal processing mechanism is thought to be a mirror image of the other.We previously reported that the immunohistochemical distribution of the subset of P2X2-purinoceptors differs between the ON and OFF cholinergic amacrine cells.Here, we investigated whether ATP activates P2-purinoceptors and modulates the physiological function of the mouse retina.We also examined if signal processing by P2-purinoceptors is pathway-specific.ATP activated both ON-and OFF-cholinergic amacrine cells.However, responses in OFF-cholinergic amacrine cells were greater than those in ON-cholinergic amacrine cells.Pharmacological studies in OFF-cholinergic amacrine cells showed that the response of OFF-cholinergie amacrine cells is mediated P2X2-purinoceptors.ATP increased GABAergic IPSCs in OFF-but not ON-cholinergic amacrine ceils.The increase in GABAergic IPSCs was mediated by P2-purinoceptors.P2-purinoceptor-mediated signals suppressed OFF ganglion ceils but activated ON ganglion cells.Our findings indicate that purinergic signal processing of the ON and OFF pathways is pathway-specific but not a mirror image of the other.