Long-term potentiation in the hippocampal CA1 region in the presence of N-methyl-D-aspartate receptor antagonists.

The present study deals with the question of whether L-type voltage-gated calcium channels can support the induction of input specific long-term potentiation. Tetanus-induced potentiation of synaptic transmission was examined in the CA1 region of normal and disinhibited guinea-pig hippocampal slices. It was found that afferent tetanization in the presence of 50 microM of the N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid led to a prolonged input specific potentiation. This potentiation was found only in disinhibited slices, its induction required cooperativity, and it was associated with an increase in the early part of the field excitatory postsynaptic potential initial slope. It was not affected by the L-type voltage-gated calcium channel blocker nifedipine, but it was reduced when D(-)-2-amino-5-phosphonopentanoic acid was supplemented with other N-methyl-D-aspartate receptor antagonists. The present study also examined a potentiation that was not restricted to the activated synapses and that was not associated with an increase in the early part of the field excitatory postsynaptic potential initial slope. This potentiation was blocked by the L-type voltage-gated calcium channel antagonist nifedipine. It is concluded that calcium influx through L-type voltage-gated calcium channels participates in the generation of a prolonged potentiation, but not of the input specific N-methyl-D-aspartate receptor-dependent long-term potentiation. The results also suggest that high concentrations of D(-)-2-amino-5-phosphonopentanoic acid can be insufficient to fully prevent N-methyl-D-aspartate receptor activation by strong afferent tetanization in the disinhibited slice.