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dc.contributor.authorWall, M.J.
dc.contributor.authorCollins, D.R.
dc.contributor.authorChery, S.L.
dc.contributor.authorAllen, Z.D.
dc.contributor.authorPastuzyn, E.D.
dc.contributor.authorGeorge, A.J.
dc.contributor.authorNikolova, V.D.
dc.contributor.authorMoy, S.S.
dc.contributor.authorPhilpot, B.D.
dc.contributor.authorShepherd, J.D.
dc.contributor.authorMuller, Jurgen
dc.contributor.authorEhlers, M.D.
dc.contributor.authorMabb, A.M.
dc.contributor.authorCorrêa, Sonia A.L.
dc.date.accessioned2018-06-18T13:28:48Z
dc.date.available2018-06-18T13:28:48Z
dc.date.issued2018-06
dc.identifier.citationWall MJ, Collins DR, Chery SL et al (2018) The temporal dynamics of Arc expression regulate cognitive flexibility. Neuron. 98(6): 1124-1132.e7en_US
dc.identifier.urihttp://hdl.handle.net/10454/16201
dc.descriptionYesen_US
dc.description.abstractNeuronal activity regulates the transcription and translation of the immediate-early gene Arc/Arg3.1, a key mediator of synaptic plasticity. Proteasomedependent degradation of Arc tightly limits its temporal expression, yet the significance of this regulation remains unknown. We disrupted the temporal control of Arc degradation by creating an Arc knockin mouse (ArcKR) where the predominant Arc ubiquitination sites were mutated. ArcKR mice had intact spatial learning but showed specific deficits in selecting an optimal strategy during reversal learning. This cognitive inflexibility was coupled to changes in Arc mRNA and protein expression resulting in a reduced threshold to induce mGluR-LTD and enhanced mGluR-LTD amplitude. These findings show that the abnormal persistence of Arc protein limits the dynamic range of Arc signaling pathways specifically during reversal learning. Our work illuminates how the precise temporal control of activity-dependent molecules, such as Arc, regulates synaptic plasticity and is crucial for cognition.en_US
dc.description.sponsorshipOpen access funded by Biotechnology and Biological Sciences Research Councilen_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1016/j.neuron.2018.05.012en_US
dc.rights©2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).en_US
dc.subjectArc/Arg3.1en_US
dc.subjectArc/Arg3.1 turnoveren_US
dc.subjectAMPA receptor traffickingen_US
dc.subjectSynaptic plasticityen_US
dc.subjectmGluR-LTDen_US
dc.subjectBarnes mazeen_US
dc.subjectReversal learningen_US
dc.subjectCognitive flexibilityen_US
dc.subjectUbiquitinen_US
dc.titleThe temporal dynamics of Arc expression regulate cognitive flexibilityen_US
dc.status.refereedYesen_US
dc.date.Accepted2018-05-04
dc.date.application2018-05-31
dc.typeArticleen_US
dc.type.versionPublished versionen_US
refterms.dateFOA2018-07-29T02:31:18Z


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