%0 Journal Article
%T MGluR5 Mediates the Interaction between Late-LTP, Network Activity, and Learning
%A Arthur Bikbaev
%A Sergey Neyman
%A Richard Teke Ngomba
%A Jeffrey Conn
%A Ferdinando Nicoletti
%A Denise Manahan-Vaughan
%J PLOS ONE
%D 2008
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0002155
%X 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¨C10 Hz) and gamma (30¨C100 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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0002155