| Online-Ressource |
Verfasst von: | Aloisi, Elisabetta [VerfasserIn]  |
| Tappe-Theodor, Anke [VerfasserIn]  |
Titel: | Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice |
Verf.angabe: | Elisabetta Aloisi, Katy Le Corf, Julien Dupuis, Pei Zhang, Melanie Ginger, Virginie Labrousse, Michela Spatuzza, Matthias Georg Haberl, Lara Costa, Ryuichi Shigemoto, Anke Tappe-Theodor, Filippo Drago, Pier Vincenzo Piazza, Christophe Mulle, Laurent Groc, Lucia Ciranna, Maria Vincenza Catania & Andreas Frick |
E-Jahr: | 2017 |
Jahr: | 24 October 2017 |
Umfang: | 14 S. |
Fussnoten: | Gesehen am 03.05.2018 |
Titel Quelle: | Enthalten in: Nature Communications |
Ort Quelle: | [London] : Nature Publishing Group UK, 2010 |
Jahr Quelle: | 2017 |
Band/Heft Quelle: | 8(2017) Artikel-Nummer 1103, 14 Seiten |
ISSN Quelle: | 2041-1723 |
Abstract: | Metabotropic glutamate receptor subtype 5 (mGluR5) is crucially implicated in the pathophysiology of Fragile X Syndrome (FXS); however, its dysfunction at the sub-cellular level, and related synaptic and cognitive phenotypes are unexplored. Here, we probed the consequences of mGluR5/Homer scaffold disruption for mGluR5 cell-surface mobility, synaptic N-methyl-D-aspartate receptor (NMDAR) function, and behavioral phenotypes in the second-generation Fmr1 knockout (KO) mouse. Using single-molecule tracking, we found that mGluR5 was significantly more mobile at synapses in hippocampal Fmr1 KO neurons, causing an increased synaptic surface co-clustering of mGluR5 and NMDAR. This correlated with a reduced amplitude of synaptic NMDAR currents, a lack of their mGluR5-activated long-term depression, and NMDAR/hippocampus dependent cognitive deficits. These synaptic and behavioral phenomena were reversed by knocking down Homer1a in Fmr1 KO mice. Our study provides a mechanistic link between changes of mGluR5 dynamics and pathological phenotypes of FXS, unveiling novel targets for mGluR5-based therapeutics. |
DOI: | doi:10.1038/s41467-017-01191-2 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Kostenfrei: Volltext: http://dx.doi.org/10.1038/s41467-017-01191-2 |
| DOI: https://doi.org/10.1038/s41467-017-01191-2 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Animals |
| Cognition |
| Disease Models, Animal |
| Female |
| Fragile X Mental Retardation Protein |
| Fragile X Syndrome |
| Hippocampus |
| Humans |
| Male |
| Mice |
| Mice, Inbred C57BL |
| Mice, Knockout |
| Neuronal Plasticity |
| Receptor, Metabotropic Glutamate 5 |
| Receptors, N-Methyl-D-Aspartate |
| Synapses |
K10plus-PPN: | 1572573236 |
Verknüpfungen: | → Zeitschrift |
Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice / Aloisi, Elisabetta [VerfasserIn]; 24 October 2017 (Online-Ressource)