MGluR5 Mediates the Interaction between Late-LTP, Network Activity, and Learning

Hdl Handle:
http://hdl.handle.net/10675.2/564
Title:
MGluR5 Mediates the Interaction between Late-LTP, Network Activity, and Learning
Authors:
Bikbaev, Arthur ( 0000-0003-3503-086X ) ; Neyman, Sergey; Ngomba, Richard Teke; Conn, Jeffrey; Nicoletti, Ferdinando; Manahan-Vaughan, Denise
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 (5â 10 Hz) and gamma (30â 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.
Editors:
Tsien, Joe Z.
Citation:
PLoS ONE. 2008 May 14; 3(5):e2155
Issue Date:
14-May-2008
URI:
http://hdl.handle.net/10675.2/564
DOI:
10.1371/journal.pone.0002155
PubMed ID:
18478073
PubMed Central ID:
PMC2364645
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Neurology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorBikbaev, Arthuren_US
dc.contributor.authorNeyman, Sergeyen_US
dc.contributor.authorNgomba, Richard Tekeen_US
dc.contributor.authorConn, Jeffreyen_US
dc.contributor.authorNicoletti, Ferdinandoen_US
dc.contributor.authorManahan-Vaughan, Deniseen_US
dc.contributor.editorTsien, Joe Z.-
dc.date.accessioned2012-10-26T16:26:42Z-
dc.date.available2012-10-26T16:26:42Z-
dc.date.issued2008-05-14en_US
dc.identifier.citationPLoS ONE. 2008 May 14; 3(5):e2155en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid18478073en_US
dc.identifier.doi10.1371/journal.pone.0002155en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/564-
dc.description.abstractHippocampal 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 (5â 10 Hz) and gamma (30â 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.en_US
dc.rightsBikbaev et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectNeuroscience/Animal Cognitionen_US
dc.subjectNeuroscience/Behavioral Neuroscienceen_US
dc.subjectNeuroscience/Neuronal Signaling Mechanismsen_US
dc.titleMGluR5 Mediates the Interaction between Late-LTP, Network Activity, and Learningen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2364645en_US
dc.contributor.corporatenameDepartment of Neurology-
dc.contributor.corporatenameCollege of Graduate Studies-
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