AbstractPurposeRegulation of synaptic transmission at the rod synaptic terminal, between rods and rod bipolar cells (RBC) and horizontal cells (HC) is not well understood. The RBC depolarize as a consequence of the decrease in the calcium regulated glutamate release by the rod axon terminal. This effect is mediated by mGluR6 receptors coupled to Gi‐TRPM1 expressed in the RBC. We propose to investigate, in living animals, the modulatory effect by GABAergic HC on this synaptic transmission by means of electroretinogram (ERG) recordings.MethodsBinocular ERG were obtained from C57BL6/J adult mice in response to low intensity full field light stimuli (0.01 cd·s·m−2) (rod response). The right eye of each animal was injected with 1 μl of phosphate buffer solution (PBS) containing either GABA (100 mm), Glutamate (100 mm), Bicuculline (10 mm), DNQX (30 mm), APB (25 mm), Hepes (100 mm) or a combination of these drugs. The left eye of each animal was injected with 1 μl of PBS. Burian‐Allen corneal electrodes were used and responses from both eyes were compared.ResultsThe intraocular injection of APB produces the abolition of the rod response, which is explained by continued activation of mGluR6 receptors by APB. Stimulation by GABA and/or glutamate of membrane receptors expressed in HC produces a significant increase in the rod response (p < 0.05), while their antagonists (Bicuculline and DNQX) produce a significant response decrease (p < 0.05). These effects can only be explained by changes in the pH of the synaptic cleft, since the acidification of the synaptic space produces the blockage of the calcium channels expressed in the axon terminal of the rods. The acidification mechanism is justified since the intraocular injection of Hepes produces the same effect as the inhibition of HC.ConclusionRegulation of the pH in the triad of rod terminal synaptic cleft by GABA receptors seems to be an effective mechanism to control signal transmission from the photoreceptors to RBC.