The effect of acidic amino acid antagonists on synaptic transmission in the hippocampal formation in vitro.

Published

Journal Article

The effects on synaptic efficacy of the putative acidic amino acid antagonists, 2-amino-4-phosphonobutyric acid (APB), 2-amino-3-phosphonopropionic acid (APP), 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) and glutamic acid diethyl ester (GDEE), were tested by bath application to the hippocampal slice preparation. On the basis of previous work, we hypothesized that APB, HA-966 and GDEE might antagonize synaptic responses to either glutamate or aspartate, but APP should antagonize only synaptic responses to aspartate. APB and HA-966 reduced the amplitude of the extracellular EPSP recorded during stimulation of the perforant path fibers, but APP and GDEE were without effect. APB, APP and HA-966, but not GDEE, consistently inhibited transmission at Schaffer collateral and commissural synapses. The mossy fiber evoked extracellular EPSP was unaffected by these agents. At the concentrations used in this study (usually 2.5 mM) none of these drugs affected the amplitude of presynaptic fiber potentials or antidromic responses, indicating that they probably acted at synapses. The spontaneous activity of hippocampal pyramidal cells, but not of dentate granule cells, increased in the presence of 2.5 mM APB. The amplitude of the population spike generated by Schaffer commissural stimulation initially increased following introduction of APB into the medium and then declined in parallel with the extracellular EPSP. In addition, APB reduced the duration of recurrent inhibition during the period when pyramidal cell firing was enhanced. These results can be explained by an antagonism at the synapse between pyramidal cell and inhibitory interneuron.

Full Text

Duke Authors

Cited Authors

  • White, WF; Nadler, JV; Cotman, CW

Published Date

  • March 23, 1979

Published In

Volume / Issue

  • 164 /

Start / End Page

  • 177 - 194

PubMed ID

  • 218685

Pubmed Central ID

  • 218685

International Standard Serial Number (ISSN)

  • 0006-8993

Digital Object Identifier (DOI)

  • 10.1016/0006-8993(79)90014-3

Language

  • eng

Conference Location

  • Netherlands