The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility

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
Divisions: 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: Biochemistry, Genetics and Molecular Biology(all),Chemistry(all),Physics and Astronomy(all)
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
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.

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License: Creative Commons Attribution


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