Interaction between the serotoninergic and GABAergic systems in frog retina as revealed by electroretinogram

Functional interactions between serotoninergic and GABAergic systems in the vertebrate retina are largely unknown. In this study, the effects of isolated or combined stimulation of the serotonin receptors (with 100 μM serotonin) and ionotropic GABAA and GABAC receptors (with 5 mM TACA) on the electroretinographic (ERG) ON (b‑wave) and OFF (d‑wave) responses were investigated in frog eyecup preparations. It was found that serotonin alone produced a significant enhancement of the b‑ and d‑wave amplitude, while TACA alone caused its marked diminution. The relative amplitude diminution, caused by the TACA treatment, was significantly smaller when TACA was applied on the background of the fully developed serotonin effect. This result suggests that the retinal serotoninergic system could diminish the effects of ionotropic GABA receptor activation on the ERG wave generator mechanisms. In order to separately evaluate the effects of the GABAC receptor activation, in a subset of experiments the effects of TACA or TACA + serotonin were tested during GABAA receptor blockade with 100 μM bicuculline. Bicuculline alone caused a marked increase of the b‑ and d‑wave amplitude. The stimulation of GABAC receptors (with TACA) during bicuculline action produced a strong diminution of the b‑ and d‑wave amplitudes. Similar relative decrease of the b‑wave amplitude was produced when TACA was applied in combination with serotonin, while the relative decrease of the d‑wave amplitude was less pronounced during treatment with serotonin + TACA than TACA alone. Our results demonstrate that there is an ON/OFF asymmetry in the receptors involved in the presumed interactions between serotoninergic and GABAergic systems. Serotonin may decrease the effects of GABAA receptor activation in the ON pathway, while it may decrease the effects of both GABAA and GABAC receptor activation in the OFF pathway.