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

Bikbaev, A., Neyman, S., Ngomba, Richard , Conn, J., Nicoletti, F. and Manahan-Vaughan, D. (2008) MGluR5 mediates the interaction between late-LTP, network activity, and learning. PLoS ONE, 3 (5). ISSN 1932-6203

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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.

Keywords:2 methyl 6 (phenylethynyl)pyridine, metabotropic receptor 1, metabotropic receptor 5, 6 methyl 2 (phenylethynyl)pyridine, 6-methyl-2-(phenylethynyl)pyridine, amino acid receptor blocking agent, metabotropic receptor, pyridine derivative, allosterism, animal experiment, animal model, animal tissue, article, controlled study, dentate gyrus, gamma rhythm, hippocampus, hypothesis, learning disorder, long term potentiation, male, memory disorder, nerve cell network, nerve cell plasticity, neuromodulation, newborn, nonhuman, pathogenesis, protein expression, rat, spatial memory, theta rhythm, animal, drug antagonism, drug effect, learning, memory, physiology, Wistar rat, Allosteric Regulation, Animals, Excitatory Amino Acid Antagonists, Long-Term Potentiation, Pyridines, Rats, Rats, Wistar, Receptors, Metabotropic Glutamate
Subjects:B Subjects allied to Medicine > B210 Pharmacology
B Subjects allied to Medicine > B140 Neuroscience
Divisions:College of Science > School of Pharmacy
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ID Code:22158
Deposited On:12 Feb 2016 12:13

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