Kainate receptors depress excitatory synaptic transmission at CA3→CA1 synapses in the hippocampus via a direct presynaptic action

Matthew Frerking, D. Schmitz, Q. Zhou, J. Johansen, R. A. Nicoll

Research output: Contribution to journalArticle

127 Scopus citations


Kainate receptor activation depresses synaptic release of neurotransmitter at a number of synapses in the CNS. The mechanism underlying this depression is controversial, and both ionotropic and metabotropic mechanisms have been suggested. We report here that the AMPA/kainate receptor agonists domoate (DA) and kainate (KA) cause a presynaptic depression of glutamatergic transmission at CA3→CA1 synapses in the hippocampus, which is not blocked by the AMPA receptor antagonist GYKI 53655 but is blocked by the AMPA/KA receptor antagonist CNQX. Neither a blockade of interneuronal discharge nor antagonists of several neuromodulators affect the depression, suggesting that it is not the result of indirect excitation and subsequent release of a neuromodulator. Presynaptic depolarization, achieved via increasing extracellular K+, caused a depression of the presynaptic fiber volley and an increase in the frequency of miniature EPSCs. Neither effect was observed with DA, suggesting that DA does not depress transmission via a presynaptic depolarization. However, the effects of DA were abolished by the G-protein inhibitors N-ethylmaleimide and pertussis toxin. These results suggest that KA receptor activation depresses synaptic transmission at this synapse via a direct, presynaptic, metabotropic action.

Original languageEnglish (US)
Pages (from-to)2958-2966
Number of pages9
JournalJournal of Neuroscience
Issue number9
Publication statusPublished - May 1 2001
Externally publishedYes



  • CA1
  • Domoate
  • Hippocampus
  • Kainate
  • Metabotropic
  • Presynaptic

ASJC Scopus subject areas

  • Neuroscience(all)

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