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

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Abstract

The network mechanisms underlying how inhibitory circuits regulate ON‐ and OFF‐responses (the b‐ and d‐waves) in the electroretinogram (ERG) remains 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 (i) L‐APB blocked the b‐wave, indicating that the b‐wave arises from the activity of ON‐bipolar cells (BCs) expressing type 6 metabotropic glutamate receptors; (ii) 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; (iii) SR 95531 augmented both the b‐ and the d‐wave, indicating that GABAergic lateral inhibitory circuits inhibit both ON‐ and OFF‐BC pathways; (iv) 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 (v) 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.

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