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dc.contributor.authorKrueger, Dilja
dc.contributor.authorOsterweil, Emily
dc.contributor.authorChen, Stephanie P.
dc.contributor.authorTye, Lynne D.
dc.contributor.authorBear, Mark
dc.date.accessioned2011-09-21T15:16:36Z
dc.date.available2011-09-21T15:16:36Z
dc.date.issued2011-02
dc.date.submitted2010-09
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/1721.1/65898
dc.description.abstractAmong the hallmark phenotypes reported in individuals with fragile X syndrome (FXS) are deficits in attentional function, inhibitory control, and cognitive flexibility, a set of cognitive skills thought to be associated with the prefrontal cortex (PFC). However, despite substantial clinical research into these core deficits, the PFC has received surprisingly little attention in preclinical research, particularly in animal models of FXS. In this study, we sought to investigate the molecular, cellular, and behavioral consequences of the loss of the fragile X mental retardation protein in the PFC of Fmr1 KO mice, a mouse model of FXS. We identify a robust cognitive impairment in these mice that may be related to the deficits in cognitive flexibility observed in individuals with FXS. In addition, we report that levels of proteins involved in synaptic function, including the NMDA receptor subunits NR1, NR2A, and NR2B; the scaffolding proteins PSD-95 and SAPAP3; and the plasticity-related gene Arc, are decreased in the prefrontal cortex of Fmr1 KO mice and are partly correlated with behavioral performance. Finally, we report that expression of c-Fos, a marker of neuronal activity, is decreased in the PFC of Fmr1 KO mice. Together, these data suggest that Fmr1 KO mice may represent a valuable animal model for the PFC-associated molecular, cellular, and behavioral abnormalities in FXS and that this model may be useful for testing the efficacy of therapeutic strategies aimed at treating the cognitive impairments in FXS.en_US
dc.description.sponsorshipFRAXA Research Foundationen_US
dc.description.sponsorshipNational Institute of Mental Health (U.S.)en_US
dc.description.sponsorshipEunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.)en_US
dc.description.sponsorshipSimons Foundationen_US
dc.description.sponsorshipMassachusetts Institute of Technology (Cathy M. Comeau (1987) Memorial Fund)en_US
dc.language.isoen_US
dc.publisherNational Academy of Sciences (U.S.)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1013855108en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePNASen_US
dc.titleCognitive dysfunction and prefrontal synaptic abnormalities in a mouse model of fragile X syndromeen_US
dc.typeArticleen_US
dc.identifier.citationKrueger, D. D. et al. “Cognitive dysfunction and prefrontal synaptic abnormalities in a mouse model of fragile X syndrome.” Proceedings of the National Academy of Sciences 108 (2011): 2587-2592. ©2011 by the National Academy of Sciences.en_US
dc.contributor.departmentmove to dc.description.sponsorshipen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentPicower Institute for Learning and Memoryen_US
dc.contributor.approverBear, Mark
dc.contributor.mitauthorBear, Mark
dc.contributor.mitauthorKrueger, Dilja
dc.contributor.mitauthorOsterweil, Emily
dc.contributor.mitauthorChen, Stephanie P.
dc.contributor.mitauthorTye, Lynne D.
dc.relation.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsKrueger, D. D.; Osterweil, E. K.; Chen, S. P.; Tye, L. D.; Bear, M. F.en
dc.identifier.orcidhttps://orcid.org/0000-0003-0582-2284
dspace.mitauthor.errortrue
mit.licensePUBLISHER_POLICYen_US


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