MGluR5 mediates the interaction between late-LTP, network activity, and learning
- 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.
| Author: | Artur BikbaevGND, Sergey NeymanGND, Richard Teke NgombaGND, Jeffrey ConnGND, Ferdinando NicolettiORCiDGND, Denise Manahan-VaughanORCiDGND |
|---|---|
| URN: | urn:nbn:de:hbz:294-76342 |
| DOI: | https://doi.org/10.1371/journal.pone.0002155 |
| Parent Title (English): | PLoS ONE |
| Publisher: | PLoS |
| Place of publication: | San Francisco |
| Document Type: | Article |
| Language: | English |
| Date of Publication (online): | 2020/11/12 |
| Date of first Publication: | 2008/05/14 |
| Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
| Volume: | 3 |
| Issue: | 5, Article e2155 |
| First Page: | e2155-1 |
| Last Page: | e2155-11 |
| Note: | Correction: MGluR5 Mediates the Interaction between Late-LTP, Network Activity, and Learning by Bikbaev A, Neyman S, Ngomba RT, Conn PJ, Nicoletti F, et al. (2008) PLOS ONE 3(5): 10.1371/annotation/58313075-ff2e-4268-9272-e942aed8d2f6. |
| Institutes/Facilities: | Institut für Physiologie, Abteilung für Neurophysiologie |
| Research Department of Neuroscience | |
| Sonderforschungsbereich 1280, A04 - Neurale Mechanismen des Extinktionslernens | |
| Sonderforschungsbereich 874, Integration und Repräsentation sensorischer Prozesse | |
| open_access (DINI-Set): | open_access |
| faculties: | International Graduate School of Neuroscience (IGSN) |
| Licence (English): |  Creative Commons - CC BY 4.0 - Attribution 4.0 International |
