TY - JOUR
T1 - Expression of FoxP2 in the basal ganglia regulates vocal motor sequences in the adult songbird
AU - Xiao, Lei
AU - Merullo, Devin P.
AU - Koch, Therese M.I.
AU - Cao, Mou
AU - Co, Marissa
AU - Kulkarni, Ashwinikumar
AU - Konopka, Genevieve
AU - Roberts, Todd F.
N1 - Funding Information:
The authors thank members of the Roberts and Konopka laboratories for discussion and comments on the manuscript, Jennifer Holdway and Matthew Harper for laboratory support, Gaurav Chattree for helping with optogenetic experiments, Maaya Ikeda and Chung Yan Cheung for advice on reverse microdialysis experiments, Clarissa Fuentes for behavioral analysis, Andrea Guerrero for animal husbandry and song recording, Ashley Anderson for cloning of FoxP2 V5, and Erich Jarvis for the original clone of zebra finch FoxP2. This research was supported by grants from the US National Institutes of Health R21DC016340 to T.F.R. and G.K., R01NS102488 to T.F.R. and R01DC014702 to G.K. DPM was supported by F32NS112557.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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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U2 - 10.1038/s41467-021-22918-2
DO - 10.1038/s41467-021-22918-2
M3 - Article
C2 - 33976169
AN - SCOPUS:85105766983
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2617
ER -