The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility. Nat Commun 2014 Aug 19;5:4701
Date
08/20/2014Pubmed ID
25134715Pubmed Central ID
PMC4143933DOI
10.1038/ncomms5701Scopus ID
2-s2.0-84907301821 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
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.
Author List
Eales KL, Palygin O, O'Loughlin T, Rasooli-Nejad S, Gaestel M, Müller J, Collins DR, Pankratov Y, Corrêa SAMESH terms used to index this publication - Major topics in bold
AnimalsCognition
Endocytosis
Female
Hippocampus
Intracellular Signaling Peptides and Proteins
Long-Term Synaptic Depression
MAP Kinase Signaling System
Male
Mice
Mice, Knockout
Models, Animal
Neuronal Plasticity
Protein Transport
Receptors, Glutamate
Synaptic Transmission
