Dopamine modulation of rod pathway signaling by suppression of GABAC feedback to rod-driven depolarizing bipolar cells.

Abstract

Reducing signal gain in the highly sensitive rod pathway prevents saturation as background light levels increase, allowing the dark-adapted retina to encode stimuli over a range of background luminances. Dopamine release is increased during light adaptation and is generally accepted to suppress rod signaling in light-adapted retinas. However, recent research has suggested that dopamine, acting through D1 receptors, could additionally produce a sensitization of the rod pathway in dim light conditions via gamma-aminobutyric acid (GABA) type C receptors. Here, we evaluated the overall activity of the depolarizing bipolar cell (DBC) population in vivo to ensure the integrity of long-distance network interactions by quantifying the b-wave of the electroretinogram in mice. We showed that dopamine, acting through D1 receptors, reduced the amplitude and sensitivity of rod-driven DBCs during light adaptation by suppressing GABA type A receptor-mediated serial inhibition onto rod DBC GABA type C receptors. Block of D1 receptors did not suppress rod-driven DBC sensitivity when GABAA -mediated serial inhibition was blocked by gabazine, suggesting that the reduction in rod-driven DBC sensitivity in the absence of D1 receptors was due to disinhibition of serial inhibitory GABAergic circuitry rather than a direct facilitatory effect on GABA release onto rod-driven DBC GABA type C receptors. Finally, the large population of GABAergic A17 wide-field amacrine cells known to maintain reciprocal inhibition with rod DBCs could be excluded from the proposed disinhibitory circuit after treatment with 5,7-dihydroxytryptamine.