Dysregulation of specialized delay/interference-dependent working memory following loss of dysbindin-1A in schizophrenia-related phenotypes

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dc.contributor.authorPetit, Emilie I.
dc.contributor.authorMichalak, Zuzanna
dc.contributor.authorCox, Rachel
dc.contributor.authorO'Tuathaigh, Colm M. P.
dc.contributor.authorClarke, Niamh
dc.contributor.authorTighe, Orna
dc.contributor.authorTalbot, Konrad
dc.contributor.authorBlake, Derek
dc.contributor.authorJoel, Josephine
dc.contributor.authorShaw, Alexander
dc.contributor.authorSheardown, Steven A.
dc.contributor.authorMorrison, Alastair D.
dc.contributor.authorWilson, Stephen
dc.contributor.authorShapland, Ellen M.
dc.contributor.authorHenshall, David C.
dc.contributor.authorKew, James N.
dc.contributor.authorKirby, Brian P.
dc.contributor.authorWaddington, John L.
dc.contributor.funderScience Foundation Ireland
dc.date.accessioned2018-07-30T10:30:32Z
dc.date.available2018-07-30T10:30:32Z
dc.date.issued2017
dc.description.abstractDysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated a novel mutant mouse, dys-1A -/-, with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment. Loss of dysbindin-1A was not associated with disruption of either long-term (olfactory) memory or spontaneous alternation behavior. However, dys-1A -/-showed enhancement in delay-dependent working memory under high levels of interference relative to controls, ie, impairment in sensitivity to the disruptive effect of such interference. These findings in dys-1A -/-provide the first evidence for differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes relevant to the pathobiology of schizophrenia. Future studies should investigate putative sex differences in these phenotypic effects.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationPetit, E. I., Michalak, Z., Cox, R., O’Tuathaigh, C. M. P., Clarke, N., Tighe, O., Talbot, K., Blake, D., Joel, J., Shaw, A., Sheardown, S. A., Morrison, A. D., Wilson, S., Shapland, E. M., Henshall, D. C., Kew, J. N., Kirby, B. P. and Waddington, J. L. (2016) 'Dysregulation of specialized delay/interference-dependent working memory following loss of dysbindin-1A in schizophrenia-related phenotypes', Neuropsychopharmacology, 42, pp. 1349–1360. doi: 10.1038/npp.2016.282en
dc.identifier.doi10.1038/npp.2016.282
dc.identifier.endpage1360
dc.identifier.issn0893-133X
dc.identifier.issued6
dc.identifier.journaltitleNeuropsychopharmacologyen
dc.identifier.startpage1349
dc.identifier.urihttps://hdl.handle.net/10468/6524
dc.identifier.volume42
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Principal Investigator Programme (PI)/07/IN.1/B960/IE/Targeted Disruption of Genes related to Neuropsychiatric Disease and Translational Phenotypes: Dysmorphogenesis Dysfunction and Drug Targets/
dc.relation.urihttps://www.nature.com/articles/npp2016282
dc.rights© 2017, American College of Neuropsychopharmacology. All rights reserved. This is the Accepted Manuscript of an article published by Nature Publishing Group in Neuropsychopharmacology on 16th December, 2016, available online: https://doi.org/10.1038/npp.2016.282en
dc.subjectCatechol-O-methyltransferaseen
dc.subjectHilar mossy cellsen
dc.subjectSdy mutant miceen
dc.subjectSusceptibility geneen
dc.subjectSex-differencesen
dc.subjectHippocampal-formationen
dc.subjectPrefrontal cortexen
dc.subjectMessenger-rnaen
dc.subjectDentate gyrusen
dc.subjectDTNBP1 geneen
dc.titleDysregulation of specialized delay/interference-dependent working memory following loss of dysbindin-1A in schizophrenia-related phenotypesen
dc.typeArticle (peer-reviewed)en
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