Blockade of amino acid‐induced depolarizations and inhibition of excitatory post‐synaptic potentials in rat dentate gyrus.

Abstract

Excitatory post-synaptic potentials (EPSP) evoked by stimulation of the medial perforant path and depolarizations induced by excitatory amino acids were recorded from granule cells in the preparation of the hippocampal slice from the rat. The effects of (.+-.)-2-amino-5-phosphonovalerate (APV), .gamma.-D-glutamylglycine (.gamma.DGG) and cis-2,3-piperidinedicarboxylate (PDA), antagonists of excitatory amino acids on these phenomena were compared. .gamma.DGG was the most effective antagonist of the EPSP. Its action was reversible and not associated with any change in the passive membrane properties of the granule cells or in the apparent reversal potential of the EPSP. Quantal analysis showed that the reduction in the EPSP paralleled the decrease in quantal size rather than quantal content, confirming a post-synaptic site of the action of .gamma.DGG. The potency of .gamma.DGG against the exogenous agonists was N-methyl-D-aspartate > kainate .gtoreq. quisqualate. APV had very little effect on the EPSP but was a selective antagonist of N-methyl-D-aspartate-induced depolarizations. PDA depolarized granule cells and increased their membrane input resistance. Although .gamma.DGG was a potent antagonist of both glutamate- and aspartate-induced depolarizations, no clear pattern of specificity could be found. The action of glutamate was unaffected by APV. The receptor for the transmitter at the synapses formed by the fibers of the perforant path with the granule cells is of the quisqualate and/or kainate type. The present data are consistent with the biochemical evidence that glutamate may be the endogenous transmitter at this synapse.