COACTIVATION OF METABOTROPIC GLUTAMATE AND N-METHYL-D-ASPARTATE RECEPTORS IS INVOLVED IN MECHANISMS OF LONG-TERM POTENTIATION MAINTENANCE IN RAT HIPPOCAMPAL CA1 NEURONS

Slices of hippocampal area CA] in the rat were employed to test the hypothesis that the activation of metabotropic glutamate receptors during tetanization is necessary for the late maintenance of long-term potentiation. If the metabotropic glutamate receptor antagonist L-2-amino-3-phosphonopropionate was present during tetanization, post-tetanic and early long-term potentiation of the population spike as well as field excitatory postsynaptic potential developed almost normally. However, 100 min after tetanization, long-term potentiation of the field excitatory postsynaptic potential decreased in an irreversible manner. The same concentration of D-2-amino-3-phosphonopropionate was ineffective. If L-2-amino-3-phosphonopropionate was applied 120 min after tetanization, it did not influence long-term potentiation. The presence of the metabotropic glutamate receptor agonist trans-D,L-1-aminocyclopentane-1,3-dicarboxylic acid during tetanization weakly enhanced the slope of field excitatory postsynaptic potential long-term potentiation. The influence Of L-2-amino-3-phosphonopropionate and D,L-1-aminocyclopentane-1,3-dicarboxylic acid on ionotropic glutamate receptors was studied using whole-cell voltage-clamp and pressure application techniques. No effect Of L-2-amino-3-phosphonopropionate on either early or late components of excitatory postsynaptic currents could be detected at the concentration used to block long-term potentiation. It is therefore unlikely that the effect Of L-2-amino-3-phosphonopropionate on long-term potentiation is due to an interaction with N-methyl-D-aspartate receptors or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors. However, bath-applied 1S,3R-D,L-1-aminocyclo-pentane-1,3-dicarboxylic acid facilitated the N-methyl-D-aspartate-induced depolarization in response to N-methyl-D-aspartate pressure application in a reversible manner. These data suggest that besides the involvement of N-methyl-D-aspartate receptors the activation of a 2-amino-3-phosphonopropionate-sensitive metabotropic glutamate receptors during or immediately after tetanization is necessary for subsequent mechanisms responsible for the maintenance of long-term potentiation. A link between metabotropic glutamate receptors and protein kinase C activation during long-term potentiation is discussed considering the similar time course of long-term potentiation blockade after application of L-2-amino-3-phosphonopropionate and protein kinase C inhibitors.