Effects of acidic amino acid antagonists on paired-pulse potentiation at the lateral perforant path.

The glutamate analogue 2-amino-4-phosphonobutyric acid (APB) has been shown to selectively reduce synaptic transmission along the lateral portion of the perforant path input to the dentate gyrus. APB is studied here with respect to effects on paired-pulse potentiation (PPP) along the perforant path. Application of APB causes a reduction in lateral perforant path responses, but also an increase in the %PPP of that response. The effect does not result simply from reducing response size, because the amount of potentiation of matched first responses increases, and also because APB reduces the potentiated response proportionately less than a comparable first response. A similar effect is seen by decreasing extracellular calcium. Reducing lateral perforant path responses with kynurenic acid, which apparently acts on postsynaptic sites, does not have a similar effect on PPP. These results may indicate a presynaptic action of APB, possibly mediated via an effect on presynaptic calcium availability.