Structure - function relationships for gamma-substituted glutamate analogues on dentate granule cells

James F. Koerner, Rodney L. Johnson, Ronald K. Freund, Michael B. Robinson, Stephen L. Crooks

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


We previously demonstrated in the Schaffer collateral-CA1 region of the hippocampus that bath-applied agonists could be distinguished from antagonists among a group of acidic amino acid analogues by extracellular recording techniques. Here we report the use of the extracellular signs of agonist activity for discerning agonists and antagonists among several γ-substituted glutamate analogues tested in the perforant path. The two-pathway composition of the perforant path offers the advantage over CA1 in that pathway-specificity, a postulated characteristic of antagonists, may be tested. By extracellular recording, D- and L-homocysteic acid, L-serine-O-sulfate, and L-2-amino-4-(5-tetrazolyl)-butanoic acid [L-glutamate tetrazol] were identified as agonists, and all 4 analogues were more potent than L-glutamate for inhibitng synaptic field potentials. Two previously identified antagonists, L-2-amino-4-phosphonobutyric acid and L-O-phosphoserine, exhibited the pathway-specificity and inhibitory kinetics consistent with properties expected for antagonists; both compounds detected 3 perforant path components with the same rank in sensitivity, suggesting that they are acting on the same set of receptors.

Original languageEnglish (US)
Pages (from-to)299-309
Number of pages11
JournalBrain Research
Issue number2
StatePublished - Aug 8 1983


  • agonists
  • antagonists
  • extracellular recording
  • gamma substitution
  • glutamate analogues
  • perforant path


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