MGluR5 mediates the interaction between late-LTP, network activity, and learning

Arthur Bikbaev, Sergey Neyman, Richard Teke Ngomba, Jeffrey Conn, Ferdinando Nicoletti, Denise Manahan-Vaughan

Research output: Contribution to journalArticle

Abstract

Hippocampal synaptic plasticity and learning are strongly regulated by metabotropic glutamate receptors (mGluRs) and particularly by mGluR5. Here, we investigated the mechanisms underlying mGluR5-modulation of these phenomena. Prolonged pharmacological blockade of mGluR5 with MPEP produced a profound impairment of spatial memory. Effects were associated with 1) a reduction of mGluR1a-expression in the dentate gyrus; 2) impaired dentate gyrus LTP; 3) enhanced CA1-LTP and 4) suppressed theta (5-10 Hz) and gamma (30-100 Hz) oscillations in the dentate gyrus. Allosteric potentiation of mGluR1 after mGluR5 blockade significantly ameliorated dentate gyrus LTP, as well as suppression of gamma oscillatory activity. CA3-lesioning prevented MPEP effects on CA1-LTP, suggesting that plasticity levels in CA1 are driven by mGluR5-dependent synaptic and network activity in the dentate gyrus. These data support the hypothesis that prolonged mGluR5-inactivation causes altered hippocampal LTP levels and network activity, which is mediated in part by impaired mGluR1-expression in the dentate gyrus. The consequence is impairment of long-term learning.

Original languageEnglish
Article numbere2155
JournalPLoS One
Volume3
Issue number5
DOIs
Publication statusPublished - May 14 2008

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Bikbaev, A., Neyman, S., Ngomba, R. T., Conn, J., Nicoletti, F., & Manahan-Vaughan, D. (2008). MGluR5 mediates the interaction between late-LTP, network activity, and learning. PLoS One, 3(5), [e2155]. https://doi.org/10.1371/journal.pone.0002155