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

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 reverse...

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Bibliographic Details
Published in:Brain research 1996-09, Vol.734 (1-2), p.223-228
Main Authors: Roon, Robert J., Koerner, James F.
Format: Article
Language:English
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Summary: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 μMl-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 compoundsl-glutamate-γ-hydroxamate,d-aspartate-β-hydroxamate and the phosphonate derivativel-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 tol-α-aminoadipate blocks or reverses quisqualate sensitization, making the neurons unresponsive to depolarization by phosphonate compounds. We now report that L-a-aminoadipate also blocks or reverses the persistent depolarization of quisqualate-sensitized neurons which is induced by exposure to the hydroxamates or L-AP3.
ISSN:0006-8993
1872-6240
DOI:10.1016/0006-8993(96)00634-8