Facilitation of long-term potentiation by prior activation of metabotropic glutamate receptors.

1. The influence of prior metabotropic glutamate receptor (mGluR) activation on subsequent long-term potentiation (LTP) induction was investigated with the use of the mGluR agonist 1-amino-cyclopentane-1S,3R-dicarboxylic acid (ACPD, 20 microM). Field potential recordings were made in the stratum radiatum of CA1 slices taken from young adult male rats and from which CA3 was routinely dissected. Theta burst stimulation (TBS) just above threshold was used to induce LTP. 2. A 10-min bath application of ACPD begun 30 min before the TBS facilitated the induction of LTP in a dose-dependent manner and resulted in an enhanced magnitude and stability of LTP. 3. ACPD did not enhance the degree of LTP induced by strong TBS, suggesting that it acts to lower the threshold for LTP induction but does not raise the ceiling on the amount of inducible LTP. 4. This priming effect by ACPD was stereo specific and lasted between 1 and 3 h. Synaptic stimulation during the ACPD application was not necessary for the enhancement of LTP. Blockade of N-methyl-D-aspartate receptors (NMDARs) during ACPD application also failed to affect the enhancement of LTP. 5. ACPD-induced priming of LTP was antagonized by L-2-amino-3-phosphonopropionic acid, suggesting an involvement of group I mGluRs. 6. ACPD-induced enhancement of LTP was not secondary to long-lasting changes in NMDAR activation or GABAAergic inhibition, because it was unaffected by the addition of picrotoxin, a gamma-aminobutyric acid-A (GABAA) receptor antagonist, and isolated NMDAR-mediated responses did not show a long-lasting enhancement in response to ACPD application. 7. These data demonstrate that activation of mGluRs can initiate persistent yet covert changes in synaptic function that facilitate the stable induction of LTP.