title: MGluR5 mediates the interaction between late-LTP, network activity, and learning.
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.
authors.affiliation: Department of Experimental Neurophysiology, Medical Faculty, Ruhr University Bochum, Bochum, Germany.
authors.forename: Arthur
authors.initials: A
authors.lastname: Bikbaev
authors.forename: Sergey
authors.initials: S
authors.lastname: Neyman
authors.forename: Richard Teke
authors.initials: RT
authors.lastname: Ngomba
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Conn
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Denise
authors.initials: D
authors.lastname: Manahan-Vaughan
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007858:Learning; D017774:Long-Term Potentiation; D008297:Male; D008568:Memory; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine