Independent control of reciprocal and lateral inhibition at the axon terminal of retinal bipolar cells

Bipolar cells (BCs), the second order neurons in the vertebrate retina, receive two types of GABAergic feedback inhibition at their axon terminal: reciprocal and lateral inhibition. It has been suggested that two types of inhibition may be mediated by different pathways. However, how each inhibition is controlled by excitatory BC output remains to be clarified. Here, we applied single/dual whole cell recording techniques to the axon terminal of electrically coupled BCs in slice preparation of the goldfish retina, and found that each inhibition was regulated independently. Activation voltage of each inhibition was different: strong output from a single BC activated reciprocal inhibition, but could not activate lateral inhibition. Outputs from multiple BCs were essential for activation of lateral inhibition. Pharmacological examinations revealed that composition of transmitter receptors and localization of Na+ channels were different between two inhibitory pathways, suggesting that different amacrine cells may mediate each inhibition. Depending on visual inputs, each inhibition could be driven independently. Model simulation showed that reciprocal and lateral inhibition cooperatively reduced BC outputs as well as background noise, thereby preserving high signal-to-noise ratio. Therefore, we conclude that excitatory BC output is efficiently regulated by the dual operating mechanisms of feedback inhibition without deteriorating the quality of visual signals.