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Publication : The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility.

First Author  Eales KL Year  2014
Journal  Nat Commun Volume  5
Pages  4701 PubMed ID  25134715
Mgi Jnum  J:272427 Mgi Id  MGI:6210020
Doi  10.1038/ncomms5701 Citation  Eales KL, et al. (2014) The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility. Nat Commun 5:4701
abstractText  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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