Persistent depression of synaptic responses occurs in quisqualate sensitized hippocampal slices after exposure to L-aspartate-β-hydroxamate

Robert J. Roon, James F. Koerner

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Exposure of slices of rat hippocampus to quisqualic acid produces an enhanced sensitivity of neurons to depolarization by other excitatory amino acid analogues, particularly amino acid phosphonates. The phosphonates may act at extracellular sites, since their depolarizing effects are rapidly reversed by washout with phosphonate-free incubation medium. We now wish to report a novel class of excitatory amino acid analogues that induce a persistent depolarization that is not reversed by washout. Exposure of quisqualate-sensitized slices of rat hippocampus to 400 μM L-aspartate-β-hydroxamate for 8 min results in the complete depression of extracellular synaptic field potentials. This depression persists for at least 1 h after washout of the hydroxamate compound. Analogous compounds L-glutamate-γ-hydroxamate, D-aspartate-β-hydroxamate and the phosphonate derivative L-2-amino-3-phosphonopropanoic acid (L-AP3) induce a similar but weaker persistent depression of the field potentials. Previous studies also demonstrated that exposure of hippocampal slices to L-α-aminoadipate blocks or reverses quisqualate sensitization, making the neurons unresponsive to depolarization by phosphonate compounds. We now report that L-α-aminoadipate also blocks or reverses the persistent depolarization of quisqualate-sensitized neurons which is induced by exposure to the hydroxamates or L-AP3.

Original languageEnglish (US)
Pages (from-to)223-228
Number of pages6
JournalBrain Research
Volume734
Issue number1-2
DOIs
StatePublished - Sep 23 1996

Bibliographical note

Funding Information:
This investigationw as supported by NIH Grant NS 17944. We wish to thank Dr. Eric W. Harris for advice on antidromicre cording,D r. Michael B. Robinson for discussions on transporst ystemsa nd inhibitorsa, nd both of these investigatorfso r critically reviewingt his paper.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Excitatory amino acid
  • Glutamate
  • Hippocampus
  • Hydroxamate
  • Quisqualate
  • Sensitization

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