Long term depression (LTD) can be induced by low frequency stimulation (LFS) as well as by agonist activation of neurotransmitter receptors. Group II metabotropic glutamate receptors (mGluRs) play an essential role in the regulation of electrically-induced LTD in the hippocampus in vivo: LTD is inhibited by antagonists, and enhanced by agonists of group II mGluRs. Here we investigated induction of LTD by activation of group II mGluRs as well as the cellular mechanisms which might mediate group II mGluR-induced LTD. Rats were implanted with electrodes to enable chronic measurement of evoked potentials from medial perforant path-dentate gyrus synapses. Drug application was made through a cannula implanted into the ipsilateral cerebral ventricle. LTD could be induced by agonist activation of either group II mGluRs, or the group II mGluR subtype, mGluR3. Both, group II mGluR-induced LTD and mGluR3-induced LTD were not abolished by mRNA/protein synthesis inhibition. Furthermore, mGluR3-induced LTD was not inhibited by NMDA receptor antagonists or altered by L-type voltage-gated calcium channel blockers. Our data suggest that sole activation of group II mGluRs can mediate LTD in vivo. Intriguingly, this form of LTD is not dependent on protein synthesis or activation of NMDA receptors.
