Eales, Katherine L., Palygin, Oleg, O'Loughlin, Thomas, Rasooli-Nejad, Seyed, Gaestel, Matthias, Müller, Jürgen, Collins, Dawn R., Pankratov, Yuriy and Corrêa, Sonia A.L. (2014). The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility. Nature Communications, 5 ,
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.
Publication DOI: | https://doi.org/10.1038/ncomms5701 |
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Divisions: | College of Health & Life Sciences > Aston Medical School |
Additional Information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ Funding: BBSRC (BB/H018344/1). Supplementary data avaialbe on the journal website. |
Uncontrolled Keywords: | General Biochemistry,Genetics and Molecular Biology,General Chemistry,General Physics and Astronomy |
Publication ISSN: | 2041-1723 |
Last Modified: | 05 Aug 2024 16:10 |
Date Deposited: | 27 Oct 2015 08:55 |
Full Text Link: | |
Related URLs: |
http://www.scop ... tnerID=8YFLogxK
(Scopus URL) |
PURE Output Type: | Article |
Published Date: | 2014-08-19 |
Authors: |
Eales, Katherine L.
Palygin, Oleg O'Loughlin, Thomas Rasooli-Nejad, Seyed Gaestel, Matthias Müller, Jürgen Collins, Dawn R. Pankratov, Yuriy Corrêa, Sonia A.L. |