The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility

Katherine L. Eales, Oleg Palygin, Thomas O'Loughlin, Seyed Rasooli-Nejad, Matthias Gaestel, Jürgen Müller, Dawn R. Collins, Yuriy Pankratov, Sonia A.L. Corrêa

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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.

Original languageEnglish
Article number4701
Number of pages16
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 19 Aug 2014

Bibliographical note

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.

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    Eales, K. L., Palygin, O., O'Loughlin, T., Rasooli-Nejad, S., Gaestel, M., Müller, J., Collins, D. R., Pankratov, Y., & Corrêa, S. A. L. (2014). The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility. Nature Communications, 5, [4701]. https://doi.org/10.1038/ncomms5701