Presynaptic effects of group III metabotropic glutamate receptors on excitatory synaptic transmission in the retina

Metabotropic glutamate receptors (mGluRs) are located in both plexiform layers in the retina and may modulate transmission between photoreceptors and bipolar cells and between bipolar and ganglion cells. We investigated whether mGluR activation modulates excitatory synaptic input to bipolar cells and ganglion cells in the salamander retinal slice preparation. The group III mGluR agonist L-2-amino-4-phosphonobutyric acid (AP4) inhibited monosynaptic excitatory postsynaptic currents (EPSCs) in ganglion cells evoked by electrical stimuli, whereas group I and group II agonists had no significant effect. AP4 reduced the frequency but not the amplitude of ganglion cell miniature EPSCs, suggesting a presynaptic action at bipolar cell terminals. AP4 also reduced ganglion cell EPSCs evoked by the offset of a light stimulus, suggesting that group III mGluRs modulate release from OFF bipolar cells. Comparison of light-evoked EPSCs in OFF bipolar cells and ganglion cells indicated that AP4 reduced ganglion cell EPSCs by acting primarily at bipolar cell terminals, and to a lesser extent at photoreceptor terminals. The group II/III mGluR antagonist (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG) blocked the effect of AP4 at bipolar cell terminals, consistent with localization of group III mGluRs at these sites. However, CPPG did not increase EPSCs at light offset, indicating that activation of group III mGluRs by synaptic glutamate does not play a large role in modulating transmission from bipolar cells to ganglion cells.