GABAergic and glycinergic systems regulate ON-OFF electroretinogram by cooperatively modulating cone pathways in the amphibian retina.

The network mechanisms underlying how inhibitory circuits regulate ON- and OFF-responses (the b- and d-waves) in the electroretinogram (ERG) remain unclear. The purpose of this study was to investigate the contribution of inhibitory circuits to the emergence of the b- and d-waves in the full-field ERG in the newt retina. To this end, we investigated the effects of several synaptic transmission blockers on the amplitudes of the b- and d-waves in the ERG obtained from newt eyecup preparations. Our results demonstrated that (a) L-APB blocked the b-wave, indicating that the b-wave arises from the activity of ON-bipolar cells (BCs) expressing type six metabotropic glutamate receptors; (b) the combined administration of UBP310/GYKI 53655 blocked the d-wave, indicating that the d-wave arises from the activity of OFF-BCs expressing kainate-/AMPA-receptors; (c) SR 95531 augmented both the b- and the d-wave, indicating that GABAergic lateral inhibitory circuits inhibit both ON- and OFF-BC pathways; (d) the administration of strychnine in the presence of SR 95531 attenuated the d-wave, and this attenuation was prevented by blocking ON-pathways with L-APB, which indicated that the glycinergic inhibition of OFF-BC pathway is downstream of the GABAergic inhibition of the ON-system; and (e) the glycinergic inhibition from the ON- to the OFF-system widens the response range of OFF-BC pathways, specifically in the absence of GABAergic lateral inhibition. Based on these results, we proposed a circuitry mechanism for the regulation of the d-wave and offered a tentative explanation of the circuitry mechanisms underlying ERG formation.