FACILITATION OF LONG-TERM POTENTIATION BY PRIOR ACTIVATION OF METABOTROPIC GLUTAMATE RECEPTORS

1. The influence of prior metabotropic glutamate receptor (mGluR) acti vation on subsequent long-term potentiation (LTP) induction was invest igated with the use of the mGluR agonist 1-amino-cyclopentane-1S,3R-di carboxylic acid (ACPD, 20 mu M). 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 app lication of ACPD begun 30 min before the TBS facilitated the induction of LTP in a dose-dependent manner and resulted in an enhanced magnitu de and stability of LTP. 3. ACPD did not enhance the degree of LTP ind uced by strong TBS, suggesting that it acts to lower the threshold for LTP induction but does not raise the ceiling on the amount of inducib le LTP. 4. This priming effect by ACPD was stereo specific and lasted between 1 and 3 h. Synaptic stimulation during the ACPD application wa s not necessary for the enhancement of LTP. Blockade of N-methyl-D-asp artate receptors (NMDARs) during ACPD application also failed to affec t the enhancement of LTP. 5. ACPD-induced priming of LTP was antagoniz ed by L-2-amino-3-phosphonopropionic acid, suggesting an involvement o f group I mGluRs. 6. ACPD-induced enhancement of LTP was not secondary to long-lasting changes in NMDAR activation or GABA(A) ergic inhibiti on, because it was unaffected by the addition of picrotoxin, a gamma-a minobutyric acid-A (GABA(A)) receptor antagonist, and isolated NMDAR-m ediated responses did not show a long-lasting enhancement in response to ACPD application. 7. These data demonstrate that activation of mGlu Rs can initiate persistent yet covert changes in synaptic function tha t facilitate the stable induction of LTP.