Abstract
The canonical mGluR6-Trpm1 pathway that generates the sign-inverting signal between photoreceptors and ON bipolar cells has been well described. However, one type of ON bipolar cell, the rod bipolar cell (RBC), additionally is thought to express the group I mGluRs whose function is unknown. We examined the role of group I mGluRs in mouse RBCs and here provide evidence that it controls synaptic gain between rods and RBCs. In dark-adapted conditions, the mGluR1 antagonists LY367385 and (RS)-1-Aminoindan-1,5-dicarboxylic acid, but not the mGluR5 antagonist 2-Methyl-6-(phenylethynyl)pyridine hydrochloride reduced the light-evoked responses in RBCs indicating that mGluR1, but not mGluR5, serves to potentiate RBC responses. Perturbing the downstream phospholipase C (PLC)-protein kinase C (PKC) pathway by inhibiting PLC, tightly buffering intracellular Ca2+ , or preventing its release from intracellular stores reduced the synaptic potentiation by mGluR1. The effect of mGluR1 activation was dependent upon adaptation state, strongly increasing the synaptic gain in dark-, but not in light-adapted retinas, or in the presence of a moderate background light, consistent with the idea that mGluR1 activation requires light-dependent glutamate release from rods. Moreover, immunostaining revealed that protein kinase Cα (PKCα) is more strongly expressed in RBC dendrites in dark-adapted conditions, revealing an additional mechanism behind the loss of mGluR1 potentiation. In light-adapted conditions, exogenous activation of mGluR1 with the agonist 3,5-Dihydroxyphenylglycine increased the mGluR6 currents in some RBCs and decreased it in others, suggesting an additional action of mGluR1 that is unmasked in the light-adapted state. Elevating intracellular free Ca2+ , consistently resulted in a decrease in synaptic gain. Our results provide evidence that mGluR1 controls the synaptic gain in RBCs.