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The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility
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Eales, Katherine L., Palygin, Oleg, O’Loughlin, Thomas, Rasooli-Nejad, Seyed, Gaestel, Matthias, Müller, Jürgen, Collins, Dawn R., Pankratov, Yuriy and Corrêa, Sônia A. L. (2014) The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility. Nature Communications, 5 . 4701. doi:10.1038/ncomms5701 ISSN 2041-1723.
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Official URL: http://dx.doi.org/10.1038/ncomms5701
Abstract
The interplay between long-term potentiation and long-term depression (LTD) is thought to be involved in learning and memory formation. One form of LTD expressed in the hippocampus is initiated by the activation of the group 1 metabotropic glutamate receptors (mGluRs). Importantly, mGluRs have been shown to be critical for acquisition of new memories and for reversal learning, processes that are thought to be crucial for cognitive flexibility. Here we provide evidence that MAPK-activated protein kinases 2 and 3 (MK2/3) regulate neuronal spine morphology, synaptic transmission and plasticity. Furthermore, mGluR-LTD is impaired in the hippocampus of MK2/3 double knockout (DKO) mice, an observation that is mirrored by deficits in endocytosis of GluA1 subunits. Consistent with compromised mGluR-LTD, MK2/3 DKO mice have distinctive deficits in hippocampal-dependent spatial reversal learning. These novel findings demonstrate that the MK2/3 cascade plays a strategic role in controlling synaptic plasticity and cognition.
| Item Type: | Journal Article | ||||||||
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Nature Communications | ||||||||
| Publisher: | Nature Publishing Group | ||||||||
| ISSN: | 2041-1723 | ||||||||
| Official Date: | 19 August 2014 | ||||||||
| Dates: |
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| Volume: | 5 | ||||||||
| Article Number: | 4701 | ||||||||
| DOI: | 10.1038/ncomms5701 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access (Creative Commons) |
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