The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility


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.

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Divisions: College of Health & Life Sciences > Aston Medical School
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Uncontrolled Keywords: General Biochemistry,Genetics and Molecular Biology,General Chemistry,General Physics and Astronomy
Publication ISSN: 2041-1723
Last Modified: 27 Jun 2024 08:41
Date Deposited: 27 Oct 2015 08:55
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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.



Version: Published Version

License: Creative Commons Attribution

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