METABOTROPIC GLUTAMATE RECEPTORS ARE INVOLVED IN LONG-TERM POTENTIATION IN ISOLATED SLICES OF RAT MEDIAL FRONTAL-CORTEX

The prelimbic region of medial frontal cortex in the rat receives a di rect input from the hippocampus and this functional connection is esse ntial for aspects of spatial memory. Activity-dependent changes in the effectiveness of synaptic transmission in the medial frontal cortex, namely long-term potentiation (LTP) and long-term depression (LTD) can persist for tens of minutes or hours and may be the basis of learning and memory storage. Glutamatergic activation of ionotropic receptors is required to induce both LTP and LTD. We now present evidence of the involvement of metabotropic glutamate receptors in LTP in isolated sl ices of frontal cortex. Repetitive bursts of stimulation at theta freq uencies (TBS) were applied to layer II, and monosynaptic EPSPs were mo nitored in layer V neurons of the prelimbic area. TBS was found to be more effective at inducing LTP than tetanic stimulation at 100 Hz and produced LTP that lasted >30 min in 8 out of 14 neurons. Tetanic stimu lation at 100 Hz in the presence of the N-methyl-D-aspartate (NMDA)-an tagonist 2-amino-5-phosphonopentanoate (AP5) was reported to be a reli able method of inducing LTD in prelimbic cortex (Hirsch and Crepel 199 1). However we found that this protocol did not facilitate the inducti on of LTD. The role of metabotropic glutamate receptors (mGluR) in LTP was assessed by using the selective, broad-spectrum antagonist (R, S) -alpha-methyl-4-carboxyphenylglycine (MCPG). This drug significantly r educed the incidence of LTP after TBS to only I of 14 neurons (P < 0.0 2, chi(2) test). The pooled responses to TBS in MCPG showed significan tly reduced potentiation [(P < 0.02, analysis of variance (ANOVA)]. Th e broad-spectrum mGluR gonist(1S,3R)-1-aminocyclopentane-1,3-dicarboxy lic acid (ACPD) and the selective group I agonist S-3 hydroxyphenylgly cine (S-SHPG) both produced membrane depolarization, an increase in nu mber of spikes evoked by depolarizing current pulses, and a reduction in the afterhyperpolarization. Similar effects were produced by these agonists even when synaptic transmission was blocked by use of the gam ma-aminobutyric acid-B (GABA(B)) receptor agonist, 200 mu M baclofen, which suggests that group I mGluRs are present on layer V neurons. We conclude that mGluRs participate in the production of LTP in prelimbic cortex, and that this excitatory effect could be mediated by the post synaptic group I mGluRs.