Priming stimulation of group II metabotropic glutamate receptors inhibits the subsequent induction of rat hippocampal long-term depression in vitro.

The ability of priming activation of metabotropic glutamate receptors (mGluRs) to regulate long-term depression (LTD) was studied in area CA1 of hippocampal slices taken from young adult male rats. Pharmacological activation of Group I mGluRs 30-40 min prior to low-frequency stimulation at 3 Hz failed to affect LTD. Activation of Group II mGluRs, however, significantly inhibited the LTD by >50%, while activation of Group III mGluRs had no statistically significant effect on LTD. The inhibition of LTD by activation of Group II mGluRs was even stronger when the Group II agonist was applied during the low-frequency stimulation. Because activation of Group II mGluRs is also known to inhibit LTP, the net effect of such stimulation is the induction of a metaplasticity that greatly restricts the effective range of stimuli that can evoke synaptic plasticity in the hippocampus.