PRIMING OF LONG-TERM POTENTIATION BY PRIOR ACTIVATION OF GROUP-I AND GROUP-II METABOTROPIC GLUTAMATE RECEPTORS IN THE RAT DENTATE GYRUS IN-VITRO

The role of metabotropic glutamate receptors (mGluRs) in long-term pot entiation (LTP) has remained controversial. However, it has recently b een shown that group I mGluR activation, prior to high frequency stimu lation (HFS), can facilitate or 'prime' LTP in the area CA1 of the hip pocampus. Here we report that, in the dentate gyrus in vitro, activati on of both group I and group II mGluRs primes LTP. Control LTP, 60 min after HFS was 145.4 +/- 3.6% of control. The group I mGluR agonist (R S)-2-chloro-5-hydroxyphenylglycine (CHPG, 100 mu M), resulted in LTP o f 180.1 +/- 12.1% of control, which was significantly greater than con trol LTP (n = 4; P < 0.05). The group I/II mGluR agonist 1S,3R-1-amino cyclopentate-1,3-dicarboxylic acid (1S,3R-ACPD, 10 mu M), and the grou p II mGluR agonist (2S,3S,4S)-alpha-(carboxy-cyclopropyl)-glycine (L-C CG-1, 20 mu M) also produced LTP that was significantly greater than c ontrol LTP (177.7 +/- 11.5% and 183.2 +/- 9.1% of control respectively ; n = 5; P < 0.05). The group III mGluR agonist L-2-amino-4-phosphonob utyric acid (L-AP4, 20 mu M), failed to significantly prime LTP (153.8 +/- 5.9% of control; n = 5). It also proved difficult to depotentiate the primed LTP. Following low frequency stimulation (LFS), control LT P was reduced to 101.1 +/- 3.6% of control, and to 145.0 +/- 2.1%, 141 .2 +/- 14.7% and 134.0 +/- 8.7% of control for CHPG, ACPD and L-CCG-1 primed LTP respectively. We conclude that LTP may be primed by mGluR a ctivation in the dentate gyrus and that this priming is mediated throu gh group I and II mGluRs. (C) 1998 Elsevier Science B.V. All rights re served.