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Foxp2 loss of function increases striatal direct pathway inhibition via increased GABA release
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dc.contributor.author | van Rhijn, Jon-Ruben | |
dc.contributor.author | Fisher, Simon E | |
dc.contributor.author | Vernes, Sonja C | |
dc.contributor.author | Nadif Kasri, Nael | |
dc.date.accessioned | 2021-03-02T15:30:09Z | |
dc.date.available | 2021-03-02T15:30:09Z | |
dc.date.issued | 2018-12 | |
dc.identifier.citation | van 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/s00429-018-1746-6 | en |
dc.identifier.issn | 1863-2653 | |
dc.identifier.other | PURE: 272110843 | |
dc.identifier.other | PURE UUID: a13e8850-97b0-4a79-b86b-7ba3893d63fb | |
dc.identifier.other | PubMed: 30187194 | |
dc.identifier.other | PubMedCentral: PMC6267273 | |
dc.identifier.other | ORCID: /0000-0003-0305-4584/work/86538543 | |
dc.identifier.other | Scopus: 85052934021 | |
dc.identifier.uri | https://hdl.handle.net/10023/21539 | |
dc.description | JRvR 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.abstract | Heterozygous 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.extent | 16 | |
dc.language.iso | eng | |
dc.relation.ispartof | Brain Structure and Function | en |
dc.rights | Copyright © 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.subject | Animals | en |
dc.subject | Corpus striatum/physiology | en |
dc.subject | Excitatory postsynaptic potentials | en |
dc.subject | Forkhead transcription factors/genetics | en |
dc.subject | Glutamate decarboxylase/metabolism | en |
dc.subject | Inhibitory postsynaptic potentials | en |
dc.subject | Learning/physiology | en |
dc.subject | Mice, inbred C57BL | en |
dc.subject | Mice, transgenic | en |
dc.subject | Motor skills | en |
dc.subject | Neurons/physiology | en |
dc.subject | Receptors, dopamine D1/physiology | en |
dc.subject | Repressor proteins/genetics | en |
dc.subject | Synapses/physiology | en |
dc.subject | gamma-Aminobutyric acid/physiology | en |
dc.subject | QH301 Biology | en |
dc.subject | RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry | en |
dc.subject | NDAS | en |
dc.subject.lcc | QH301 | en |
dc.subject.lcc | RC0321 | en |
dc.title | Foxp2 loss of function increases striatal direct pathway inhibition via increased GABA release | en |
dc.type | Journal article | en |
dc.description.version | Publisher PDF | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.identifier.doi | https://doi.org/10.1007/s00429-018-1746-6 | |
dc.description.status | Peer reviewed | en |
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