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An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning
Mutations in the human FOXP2 gene cause impaired speech development and linguistic deficits, which have been best characterised in a large pedigree called the KE family. The encoded protein is highly conserved in many vertebrates and is expressed in homologous brain regions required for sensorimotor...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481071/ https://www.ncbi.nlm.nih.gov/pubmed/21876543 http://dx.doi.org/10.1038/mp.2011.105 |
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author | French, C A Jin, X Campbell, T G Gerfen, E Groszer, M Fisher, S E Costa, R M |
author_facet | French, C A Jin, X Campbell, T G Gerfen, E Groszer, M Fisher, S E Costa, R M |
author_sort | French, C A |
collection | PubMed |
description | Mutations in the human FOXP2 gene cause impaired speech development and linguistic deficits, which have been best characterised in a large pedigree called the KE family. The encoded protein is highly conserved in many vertebrates and is expressed in homologous brain regions required for sensorimotor integration and motor-skill learning, in particular corticostriatal circuits. Independent studies in multiple species suggest that the striatum is a key site of FOXP2 action. Here, we used in vivo recordings in awake-behaving mice to investigate the effects of the KE-family mutation on the function of striatal circuits during motor-skill learning. We uncovered abnormally high ongoing striatal activity in mice carrying an identical mutation to that of the KE family. Furthermore, there were dramatic alterations in striatal plasticity during the acquisition of a motor skill, with most neurons in mutants showing negative modulation of firing rate, starkly contrasting with the predominantly positive modulation seen in control animals. We also observed striking changes in the temporal coordination of striatal firing during motor-skill learning in mutants. Our results indicate that FOXP2 is critical for the function of striatal circuits in vivo, which are important not only for speech but also for other striatal-dependent skills. |
format | Online Article Text |
id | pubmed-3481071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-34810712012-10-26 An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning French, C A Jin, X Campbell, T G Gerfen, E Groszer, M Fisher, S E Costa, R M Mol Psychiatry Original Article Mutations in the human FOXP2 gene cause impaired speech development and linguistic deficits, which have been best characterised in a large pedigree called the KE family. The encoded protein is highly conserved in many vertebrates and is expressed in homologous brain regions required for sensorimotor integration and motor-skill learning, in particular corticostriatal circuits. Independent studies in multiple species suggest that the striatum is a key site of FOXP2 action. Here, we used in vivo recordings in awake-behaving mice to investigate the effects of the KE-family mutation on the function of striatal circuits during motor-skill learning. We uncovered abnormally high ongoing striatal activity in mice carrying an identical mutation to that of the KE family. Furthermore, there were dramatic alterations in striatal plasticity during the acquisition of a motor skill, with most neurons in mutants showing negative modulation of firing rate, starkly contrasting with the predominantly positive modulation seen in control animals. We also observed striking changes in the temporal coordination of striatal firing during motor-skill learning in mutants. Our results indicate that FOXP2 is critical for the function of striatal circuits in vivo, which are important not only for speech but also for other striatal-dependent skills. Nature Publishing Group 2012-11 2011-08-30 /pmc/articles/PMC3481071/ /pubmed/21876543 http://dx.doi.org/10.1038/mp.2011.105 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article French, C A Jin, X Campbell, T G Gerfen, E Groszer, M Fisher, S E Costa, R M An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning |
title | An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning |
title_full | An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning |
title_fullStr | An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning |
title_full_unstemmed | An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning |
title_short | An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning |
title_sort | aetiological foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481071/ https://www.ncbi.nlm.nih.gov/pubmed/21876543 http://dx.doi.org/10.1038/mp.2011.105 |
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