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Expression of FoxP2 in the basal ganglia regulates vocal motor sequences in the adult songbird

Disruption of the transcription factor FoxP2, which is enriched in the basal ganglia, impairs vocal development in humans and songbirds. The basal ganglia are important for the selection and sequencing of motor actions, but the circuit mechanisms governing accurate sequencing of learned vocalization...

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Autores principales: Xiao, Lei, Merullo, Devin P., Koch, Therese M. I., Cao, Mou, Co, Marissa, Kulkarni, Ashwinikumar, Konopka, Genevieve, Roberts, Todd F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113549/
https://www.ncbi.nlm.nih.gov/pubmed/33976169
http://dx.doi.org/10.1038/s41467-021-22918-2
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author Xiao, Lei
Merullo, Devin P.
Koch, Therese M. I.
Cao, Mou
Co, Marissa
Kulkarni, Ashwinikumar
Konopka, Genevieve
Roberts, Todd F.
author_facet Xiao, Lei
Merullo, Devin P.
Koch, Therese M. I.
Cao, Mou
Co, Marissa
Kulkarni, Ashwinikumar
Konopka, Genevieve
Roberts, Todd F.
author_sort Xiao, Lei
collection PubMed
description Disruption of the transcription factor FoxP2, which is enriched in the basal ganglia, impairs vocal development in humans and songbirds. The basal ganglia are important for the selection and sequencing of motor actions, but the circuit mechanisms governing accurate sequencing of learned vocalizations are unknown. Here, we show that expression of FoxP2 in the basal ganglia is vital for the fluent initiation and termination of birdsong, as well as the maintenance of song syllable sequencing in adulthood. Knockdown of FoxP2 imbalances dopamine receptor expression across striatal direct-like and indirect-like pathways, suggesting a role of dopaminergic signaling in regulating vocal motor sequencing. Confirming this prediction, we show that phasic dopamine activation, and not inhibition, during singing drives repetition of song syllables, thus also impairing fluent initiation and termination of birdsong. These findings demonstrate discrete circuit origins for the dysfluent repetition of vocal elements in songbirds, with implications for speech disorders.
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spelling pubmed-81135492021-05-14 Expression of FoxP2 in the basal ganglia regulates vocal motor sequences in the adult songbird Xiao, Lei Merullo, Devin P. Koch, Therese M. I. Cao, Mou Co, Marissa Kulkarni, Ashwinikumar Konopka, Genevieve Roberts, Todd F. Nat Commun Article Disruption of the transcription factor FoxP2, which is enriched in the basal ganglia, impairs vocal development in humans and songbirds. The basal ganglia are important for the selection and sequencing of motor actions, but the circuit mechanisms governing accurate sequencing of learned vocalizations are unknown. Here, we show that expression of FoxP2 in the basal ganglia is vital for the fluent initiation and termination of birdsong, as well as the maintenance of song syllable sequencing in adulthood. Knockdown of FoxP2 imbalances dopamine receptor expression across striatal direct-like and indirect-like pathways, suggesting a role of dopaminergic signaling in regulating vocal motor sequencing. Confirming this prediction, we show that phasic dopamine activation, and not inhibition, during singing drives repetition of song syllables, thus also impairing fluent initiation and termination of birdsong. These findings demonstrate discrete circuit origins for the dysfluent repetition of vocal elements in songbirds, with implications for speech disorders. Nature Publishing Group UK 2021-05-11 /pmc/articles/PMC8113549/ /pubmed/33976169 http://dx.doi.org/10.1038/s41467-021-22918-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Xiao, Lei
Merullo, Devin P.
Koch, Therese M. I.
Cao, Mou
Co, Marissa
Kulkarni, Ashwinikumar
Konopka, Genevieve
Roberts, Todd F.
Expression of FoxP2 in the basal ganglia regulates vocal motor sequences in the adult songbird
title Expression of FoxP2 in the basal ganglia regulates vocal motor sequences in the adult songbird
title_full Expression of FoxP2 in the basal ganglia regulates vocal motor sequences in the adult songbird
title_fullStr Expression of FoxP2 in the basal ganglia regulates vocal motor sequences in the adult songbird
title_full_unstemmed Expression of FoxP2 in the basal ganglia regulates vocal motor sequences in the adult songbird
title_short Expression of FoxP2 in the basal ganglia regulates vocal motor sequences in the adult songbird
title_sort expression of foxp2 in the basal ganglia regulates vocal motor sequences in the adult songbird
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113549/
https://www.ncbi.nlm.nih.gov/pubmed/33976169
http://dx.doi.org/10.1038/s41467-021-22918-2
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