Activation of group II metabotropic glutamate receptors results in long-term potentiation following preconditioning stimulation in the dentate gyrus.

The role of group II metabotropic glutamate receptors in the induction/expression of long-term potentiation has been investigated in the medial perforant path of the outer (infrapyramidal) blade of the rat dentate gyrus in vitro. Activation of group II metabotropic glutamate receptors by perfusion of the selective agonist LY354740 did not induce long-term potentiation or long-term depression in control. However, LY354740, applied following the induction of long-term potentiation by high frequency stimulation, resulted in additional long-term potentiation. LY354740 was only found to cause additional long-term potentiation if the pre-existing high frequency stimulation-induced long-term potentiation was sub-maximal. Although activation of metabotropic glutamate receptors was not required for induction of high frequency stimulation-induced long-term potentiation, activation of both group I and group II metabotropic glutamate receptors was required during high frequency stimulation-induced long-term potentiation in order for subsequent application of LY354740 to result in additional long-term potentiation. Thus, the long-term potentiation caused by application of LY354740 following high frequency-induced long-term potentiation was prevented if the high frequency stimulation was given in the presence of (S)-alpha-methyl-4-carboxyphenylglycine or the selective group I or group II metabotropic glutamate receptor antagonists 1-aminoindan-1,5-dicarboxylic acid or (2S)-alpha-ethylglutamic acid respectively. The long-term potentiation caused by LY354740 was also dependent upon activation of N-methyl-D-aspartate receptors during the high frequency stimulation, being blocked if high frequency stimulation was given in the presence of the N-methyl-D-aspartate receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid. The long-term potentiation resulting from activation of group II metabotropic glutamate receptors could be due either to the enhancement of the expression level of the high frequency stimulation-induced long-term potentiation, or alternatively, to a direct novel induction of long-term potentiation. In either theory, the long-term potentiation resulting from activation of group II metabotropic glutamate receptors is dependent upon prestimulation of group I and group II metabotropic glutamate receptors and N-methyl-D-aspartate receptors during the 'preconditioning high frequency stimulation'.