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dc.contributor.authorvan Rhijn, Jon-Ruben
dc.contributor.authorFisher, Simon E
dc.contributor.authorVernes, Sonja C
dc.contributor.authorNadif Kasri, Nael
dc.date.accessioned2021-03-02T15:30:09Z
dc.date.available2021-03-02T15:30:09Z
dc.date.issued2018-12
dc.identifier.citationvan Rhijn , J-R , Fisher , S E , Vernes , S C & Nadif Kasri , N 2018 , ' Foxp2 loss of function increases striatal direct pathway inhibition via increased GABA release ' , Brain Structure and Function , vol. 223 , no. 9 , pp. 4211-4226 . https://doi.org/10.1007/s00429-018-1746-6en
dc.identifier.issn1863-2653
dc.identifier.otherPURE: 272110843
dc.identifier.otherPURE UUID: a13e8850-97b0-4a79-b86b-7ba3893d63fb
dc.identifier.otherPubMed: 30187194
dc.identifier.otherPubMedCentral: PMC6267273
dc.identifier.otherORCID: /0000-0003-0305-4584/work/86538543
dc.identifier.otherScopus: 85052934021
dc.identifier.urihttp://hdl.handle.net/10023/21539
dc.descriptionJRvR is supported by an RUMC Junior Round grant from the Donders institute Ph.D. program, awarded to NNK and SCV. SCV is supported by a Marie Curie Career Integration Grant (PCIG12-GA-2012-333978) and by a Max Planck Research Group Award. SEF is supported by the Max Planck Society.en
dc.description.abstractHeterozygous mutations of the Forkhead-box protein 2 (FOXP2) gene in humans cause childhood apraxia of speech. Loss of Foxp2 in mice is known to affect striatal development and impair motor skills. However, it is unknown if striatal excitatory/inhibitory balance is affected during development and if the imbalance persists into adulthood. We investigated the effect of reduced Foxp2 expression, via a loss-of-function mutation, on striatal medium spiny neurons (MSNs). Our data show that heterozygous loss of Foxp2 decreases excitatory (AMPA receptor-mediated) and increases inhibitory (GABA receptor-mediated) currents in D1 dopamine receptor positive MSNs of juvenile and adult mice. Furthermore, reduced Foxp2 expression increases GAD67 expression, leading to both increased presynaptic content and release of GABA. Finally, pharmacological blockade of inhibitory activity in vivo partially rescues motor skill learning deficits in heterozygous Foxp2 mice. Our results suggest a novel role for Foxp2 in the regulation of striatal direct pathway activity through managing inhibitory drive.
dc.format.extent16
dc.language.isoeng
dc.relation.ispartofBrain Structure and Functionen
dc.rightsCopyright © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.en
dc.subjectAnimalsen
dc.subjectCorpus striatum/physiologyen
dc.subjectExcitatory postsynaptic potentialsen
dc.subjectForkhead transcription factors/geneticsen
dc.subjectGlutamate decarboxylase/metabolismen
dc.subjectInhibitory postsynaptic potentialsen
dc.subjectLearning/physiologyen
dc.subjectMice, inbred C57BLen
dc.subjectMice, transgenicen
dc.subjectMotor skillsen
dc.subjectNeurons/physiologyen
dc.subjectReceptors, dopamine D1/physiologyen
dc.subjectRepressor proteins/geneticsen
dc.subjectSynapses/physiologyen
dc.subjectgamma-Aminobutyric acid/physiologyen
dc.subjectQH301 Biologyen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectNDASen
dc.subject.lccQH301en
dc.subject.lccRC0321en
dc.titleFoxp2 loss of function increases striatal direct pathway inhibition via increased GABA releaseen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.identifier.doihttps://doi.org/10.1007/s00429-018-1746-6
dc.description.statusPeer revieweden


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