Surround inhibition of mammalian AII amacrine cells is generated in the proximal retina

1. Intracellular recordings were obtained from neurons in the superfused re tina-eyecup preparation of the rabbit under dark-adapted conditions. Neurot ransmitter agonists and antagonists were applied exogenously via the superf usate to dissect the synaptic pathways pharmacologically and thereby determ ine those pathways responsible for the generation of the on-centre/off-surr ound receptive fields of AII amacrine cells. 2. Application of the metabotropic glutamate receptor agonist, APE, reversi bly blocked both the on-centre and off-surround responses of AII cells. The se data were consistent with the idea that both the centre- and surround-me diated responses are derived from inputs from the presynaptic rod bipolar c ells. 3. Whereas rod bipolar cells showed on-receptive fields similar to 100 mu m across, we found no evidence for an antagonistic off-surround response usi ng light stimuli which effectively elicited the off-surrounds of AII amacri ne cells. These results indicated that the surrounds of AII cells are not d erived from rod bipolar cell inputs. 4. Application of the ionotropic glutamate receptor antagonists CNQX or DNQ X enhanced the on-centre responses of AII cells but attenuated the off-surr ound responses. These data indicated that the centre- and surround-mediated responses could not both be derived from signals crossing the rod bipolar- to-AII cell synapse. 5. Application of the glycine antagonist, strychnine, had only minor and va riable effects on AII cell responses. However, the GABA antagonists picroto xin and bicuculline enhanced the on-centre response but attenuated or compl etely blocked the off-surround response of AII cells. The GABA antagonists had no effect on the responses of horizontal cells indicating that their ef fects on AII cell responses reflected actions on inner retinal circuitry ra ther than feedback circuitry in the outer plexiform layer. 6. Application of the voltage-gated sodium channel blocker TTX enhanced the on-centre responses of AII cells but attenuated or abolished their off-sur round responses. 7. Taken together, our results suggest that the on-centre responses of AII cells result from the major excitatory drive from rod bipolar cells. Howeve r, the surround receptive fields of AII cells appear to be generated by lat eral, inhibitory signals derived from neighbouring GABAergic, on-centre ama crine cells. A model is presented whereby the S1 amacrine cells produce the surround receptive fields of AII amacrine cells via inhibitory, feedback c ircuitry to the axon terminals of rod bipolar cells.