The GluR5 subtype of kainate receptor regulates excitatory synaptic transmission in areas CA1 and CA3 of the rat hippocampus

M. Vignes, V. R.J. Clarke, M. J. Parry, D. Bleakman, D. Lodge, P. L. Ornstein, G. L. Collingridge*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

Activation of kainate receptors depresses excitatory synaptic transmission in the hippocampus. In the present study, we have utilised a GluR5 selective agonist, ATPA [(RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid], and a GluR5 selective antagonist, LY294486 [(3SR,4aRS,6SR,8aRS)-6-({[(1H-tetrazol-5-yl)methyl]oxy}methyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid], to determine whether GluR5 subunits are involved in this effect. ATPA mimicked the presynaptic depressant effects of kainate in the CA1 region of the hippocampus. It depressed reversibly AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor-mediated field excitatory postsynaptic potentials (field EPSPs) with an IC50 value of ~0.60 μM. The dual-component excitatory postsynaptic current (EPSC) and the pharmacologically isolated NMDA (N-methyl-d-aspartate) receptor-mediated EPSC were depressed to a similar extent by 2 μM ATPA (61±7% and 58±6%, respectively). Depressions were associated with an increase in the paired-pulse facilitation ratio suggesting a presynaptic locus of action. LY294486 (20 μM) blocked the effects of 2 μM ATPA on NMDA receptor-mediated EPSCs in a reversible manner. In area CA3, 1 μM ATPA depressed reversibly mossy fibre-evoked synaptic transmission (by 82±10%). The effects of ATPA were not accompanied by any changes in the passive properties of CA1 or CA3 neurones. However, in experiments where K+, rather than Cs+, containing electrodes were used, a small outward current was observed. These results show that GluR5 subunits comprise or contribute to a kainate receptor that regulates excitatory synaptic transmission in both the CA1 and CA3 regions of the hippocampus. Copyright (C) 1998 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)1269-1277
Number of pages9
JournalNeuropharmacology
Volume37
Issue number10-11
DOIs
StatePublished - Oct 1 1998

Keywords

  • ATPA
  • EPSP
  • Hippocampus
  • Kainic acid
  • LY294486
  • Mossy fibre
  • Presynaptic receptor
  • Synaptic transmission

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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