GluR7 is an essential subunit of presynaptic kainate autoreceptors at hippocampal mossy fiber synapses

Paulo S. Pinheiro, David Perrais, Françoise Coussen, Jacques Barhanin, Bernhard Bettler, Jeffrey R. Mann, João O. Malva, Stephen F. Heinemann, Christophe Mulle

Research output: Contribution to journalArticleResearchpeer-review

98 Citations (Scopus)

Abstract

Presynaptic ionotropic glutamate receptors are emerging as key players in the regulation of synaptic transmission. Here we identify GluR7, a kainate receptor (KAR) subunit with no known function in the brain, as an essential subunit of presynaptic autoreceptors that facilitate hippocampal mossy fiber synaptic transmission. GluR7-/- mice display markedly reduced short- and long-term synaptic potentiation. Our data suggest that presynaptic KARs are GluR6/GluR7 heteromers that coassemble and are localized within synapses. We show that recombinant GluR6/GluR7 KARs exhibit low sensitivity to glutamate, and we provide evidence that presynaptic KARs at mossy fiber synapses are likely activated by high concentrations of glutamate. Overall, from our data, we propose a model whereby presynaptic KARs are localized in the presynaptic active zone close to release sites, display low affinity for glutamate, are likely Ca2+-permeable, are activated by single release events, and operate within a short time window to facilitate the subsequent release of glutamate.

Original languageEnglish
Pages (from-to)12181-12186
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number29
DOIs
Publication statusPublished - 17 Jul 2007
Externally publishedYes

Keywords

  • Kainate receptors
  • Presynaptic glutamate receptors
  • Short-term plasticity
  • Synaptic plasticity

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