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

Lei Xiao, Devin P. Merullo, Therese M. I. Koch, Mou Cao, Marissa Co, Ashwinikumar Kulkarni, Genevieve Konopka and Todd F. Roberts ()
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Lei Xiao: UT Southwestern Medical Center
Devin P. Merullo: UT Southwestern Medical Center
Therese M. I. Koch: UT Southwestern Medical Center
Mou Cao: UT Southwestern Medical Center
Marissa Co: UT Southwestern Medical Center
Ashwinikumar Kulkarni: UT Southwestern Medical Center
Genevieve Konopka: UT Southwestern Medical Center
Todd F. Roberts: UT Southwestern Medical Center

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-22918-2

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