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 and Sonia A.L. Corrêa ()
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Katherine L. Eales: School of Life Sciences, University of Warwick
Oleg Palygin: School of Life Sciences, University of Warwick
Thomas O’Loughlin: School of Life Sciences, University of Warwick
Seyed Rasooli-Nejad: School of Life Sciences, University of Warwick
Matthias Gaestel: Institute of Biochemistry, Hannover Medical University
Jürgen Müller: Warwick Medical School, University of Warwick
Dawn R. Collins: Warwick Medical School, University of Warwick
Yuriy Pankratov: School of Life Sciences, University of Warwick
Sonia A.L. Corrêa: School of Life Sciences, University of Warwick

Nature Communications, 2014, vol. 5, issue 1, 1-16

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5701

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