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dc.contributor.authorPrivitera, Lucia*
dc.contributor.authorHogg, Ellen L.*
dc.contributor.authorGaestel, M.*
dc.contributor.authorWall, M.J.*
dc.contributor.authorCorrêa, Sonia A.L.*
dc.date.accessioned2019-06-05T13:21:53Z
dc.date.available2019-06-05T13:21:53Z
dc.date.issued2019-09-01
dc.identifier.citationPrivitera L, Hogg EL, Gaestel M et al (2019) The MK2 cascade regulates mGluR-dependent synaptic plasticity and reversal learning. Neuropharmacology. 155: 121-130.en_US
dc.identifier.urihttp://hdl.handle.net/10454/17110
dc.descriptionYesen_US
dc.description.abstractThe ability to either erase or update the memories of a previously learned spatial task is an essential process that is required to modify behaviour in a changing environment. Current evidence suggests that the neural representation of such cognitive flexibility involves the balancing of synaptic potentiation (acquisition of memories) with synaptic depression (modulation and updating previously acquired memories). Here we demonstrate that the p38 MAPK/MAPK-activated protein kinase 2 (MK2) cascade is required to maintain the precise tuning of long-term potentiation and long-term depression at CA1 synapses of the hippocampus which is correlated with efficient reversal learning. Using the MK2 knockout (KO) mouse, we show that mGluR-LTD, but not NMDAR-LTD, is markedly impaired in mice aged between 4 and 5 weeks (juvenile) to 7 months (mature adult). Although the amplitude of LTP was the same as in wildtype mice, priming of LTP by the activation of group I metabotropic receptors was impaired in MK2 KO mice. Consistent with unaltered LTP amplitude and compromised mGluR-LTD, MK2 KO mice had intact spatial learning when performing the Barnes maze task, but showed specific deficits in selecting the most efficient combination of search strategies to perform the task reversal. Findings from this study suggest that the mGluR-p38-MK2 cascade is important for cognitive flexibility by regulating LTD amplitude and the priming of LTP.en_US
dc.description.sponsorshipProfessor Richard Greene at the University of Bradford - startup fund to setup electrophysiological facility and Wellcome Trust 200646/Z/16/Z to S.A.L.C.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1016/j.neuropharm.2019.05.024en_US
dc.rights© 2019 Elsevier. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.en_US
dc.subjectmGluR-LTDen_US
dc.subjectmGluR-mediated priming of LTPen_US
dc.subjectReversal learningen_US
dc.subjectHippocampusen_US
dc.subjectMAP kinase signallingen_US
dc.subjectBarnes mazeen_US
dc.titleThe MK2 cascade regulates mGluR-dependent synaptic plasticity and reversal learningen_US
dc.status.refereedYesen_US
dc.date.Accepted2019-05-18
dc.date.application2019-05-23
dc.typeArticleen_US
dc.date.EndofEmbargo2020-05-24
dc.type.versionAccepted manuscripten_US
dc.description.publicnotesThe full-text of this article will be released for public view at the end of the publisher embargo on 24 May 2020.en_US
refterms.dateFOA2019-06-05T13:21:53Z


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