title: The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility.
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.
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Eales
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Oleg
authors.initials: O
authors.lastname: Palygin
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: O'Loughlin
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Seyed
authors.initials: S
authors.lastname: Rasooli-Nejad
authors.affiliation: Institute of Biochemistry, Hannover Medical University, 30625 Hannover, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gaestel
authors.affiliation: Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Müller
authors.affiliation: Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Dawn R
authors.initials: DR
authors.lastname: Collins
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Pankratov
authors.affiliation: 1] School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK [2] School of Life Sciences, University of Bradford, Bradford BD7 1DP, UK.
authors.forename: Sonia A L
authors.initials: SA
authors.lastname: Corrêa
mesh_terms: D000818:Animals; D003071:Cognition / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009473:Neuronal Plasticity / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D017470:Receptors, Glutamate; D000099190:MAP-Kinase-Activated Kinase 2; C098416:MAP-kinase-activated kinase 3