The d-wave of the zebrafish ERG derives mainly from OFF-bipolar cell activity

Purpose: The b-wave of the electroretinogram (ERG) derives from ON-bipolar cells. The contribution of OFF-bipolar cells to the ERG is not well understood. Results from mudpuppy and the Macaca monkey suggest that the d-wave of the ERG may arise as a result of OFF-bipolar cell activity. To test this idea, we investigated the effects of CNQX, a specific AMPA/kainate receptor antagonist that blocks photoreceptor to OFF-bipolar cell activity, on the photopic ERG of zebrafish. Methods: A steady, bright background was used to depress rod activity. The ERGs recorded reflected mainly cone activity and showed a prominent d-wave. ERGs of adult fish were recorded at the cornea before and after intraocular injections of CNQX (final concentrations, 15 - 90 microM), using flashes lasting 0.5 to 0.9 seconds. Results: The d-wave of the ERG was almost completely abolished by CNQX treatment. The small off response that remained had a slightly increased latency. On the other hand, the b-wave became larger and longer-lasting compared with the b-wave of the control ERG. No changes in the a-wave were observed. Conclusions: Synaptic transmission onto OFF-bipolar cells, horizontal cells, and a subset of ganglion cells is mediated by AMPA/kainate receptors. In the CNQX-treated eye, the light-responses of these cell types are presumably blocked. Since the ERG derives mainly from radially oriented, distal retinal cells, we conclude that the d-wave arises primarily from the OFF-bipolar cells. We further suppose that the increase of b-wave amplitude and the lengthening of the b-wave response after CNQX can be accounted for by suppression of OFF-bipolar cell activity.