Intracellular recordings were obtained from retinal neurons of the mudpuppy, Necturus, while superfusing the eyecup with various pharmacologic agents. In most experiments, the retina was continuously stimulated with a small spot of red light that was centered over the recording electrode and flickering at rates too fast for amphibian rods to follow. The retina was additionally stimulated intermittently with a dim, spatially diffuse background field of 520 nm wavelength. 2. In general, the dim background greatly enhanced flicker responsiveness. We (16) previously called this effect suppressive rod-cone interaction (SRCI) and showed it reflects a tonic suppressive influence on cone pathways that is removed by selective rod-light adaptation. 3. Lead chloride has been claimed to selectively block rod-related retinal responses (13, 35). While recording from horizontal cells lead chloride decreases responses to the dim, diffuse light flashes, enhances the frequency entrained response attributable to cones, and eliminates a background influence on flicker responses. 4. O-phospho-D-serine (DOP), kynurenic acid (KyA), and piperidine dicarboxylic acid are known to act on horizontal cells as antagonists of the photoreceptor neurotransmitter (26, 32, 33). In both depolarizing and hyperpolarizing bipolar cells, these agents enhance flicker responsiveness with no background present and prevent background enhancement of flicker. 5. Mudpuppy cones were found to have a receptive-field surround, which under our stimulus conditions is attributable to rod input. KyA, which is unknown to have any direct influence on photoreceptors, totally blocks this surround mechanism. This indicates that the cone-surround mechanism is attributable to horizontal cell feedback. The influence of KyA on SRCI in cones is similar to that observed in recordings from depolarizing bipolar cells. 6. Most sustained third-order neurons demonstrate SRCI. In these cells, SRCI is blocked by DOP or KyA. Most ON-OFF neurons fail to demonstrate SRCI under control circumstances. The ON-response of these cells is blocked by 2-amino-4-phosphonobutyric acid (31) which leaves the OFF-response intact. While their ON-response is blocked, ON-OFF neurons demonstrate SRCI. 7. The foregoing results indicate that SRCI reflects a tonic, inhibitory influence of horizontal cells on cone pathways that is removed by light-adapting rods. In part, SRCI must involve horizontal cell feedback onto cones. SRCI in third-order neurons appears to largely reflect distal retinal processing.
