A metabotropic glutamate receptor agonist DCG-IV suppresses synaptic transmission at mossy fiber pathway of the guinea pig hippocampus.

The effects of specific metabotropic glutamate receptor (mGluR) agonists on field excitatory postsynaptic potentials (fEPSPs) at mossy fiber-CA3 synapses were examined in guinea pig hippocampal slice preparations. Application of a novel and potent group II-selective mGluR agonist (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV; 0.1 microM) reversibly reduced the fEPSPs. Both the group III-selective agonist DL-2-amino-4-phosphonobutyric acid (AP4; 50 microM) and the broad-spectrum agonist 1S,3R-1-aminocyclopentane-1, 3-dicarboxylic acid (1S,3R-ACPD; 5 microM) also reversibly suppressed the fEPSPs. These results suggest that multiple mGluR subtypes (belonging to groups II and III) are expressed at mossy fiber synapses of the guinea pig hippocampus and activation of the receptors reduces the synaptic excitation, although we cannot exclude the possibility that guinea pig mossy fiber-CA3 synapses express a single class of mGluRs with unique pharmacological profiles.