Expression of FoxP2 in the basal ganglia regulates vocal motor sequences in the adult songbird.
Expression of FoxP2 in the basal ganglia regulates vocal motor sequences in the adult songbird.
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DOI：
10.1038/s41467-021-22918-2
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发表时间：
2021-05-11
影响因子：
16.6
通讯作者：
Roberts TF
中科院分区：
文献类型：
--
作者：
Xiao L;Merullo DP;Koch TMI;Cao M;Co M;Kulkarni A;Konopka G;Roberts TF
转录因子FoxP2富含在基底节，破坏转录因子FoxP2会损害人类和鸣禽的声音发育。基底节对于运动动作的选择和排序很重要，但控制学习发声准确排序的电路机制尚不清楚。在这里，我们证明了FoxP2在基底节的表达对于鸟鸣的流畅开始和结束以及成年后鸟鸣音节序列的维持至关重要。FoxP2基因敲除后，纹状体直接样和间接样通路中的多巴胺受体表达失衡，提示多巴胺能信号在调节发声运动序列中发挥作用。证实了这一预测，我们发现在歌唱过程中，阶段多巴胺的激活，而不是抑制，驱动了歌唱音节的重复，从而也损害了鸟鸣流畅的开始和结束。这些发现证明了鸣禽发声元素不流畅重复的离散回路来源，这与言语障碍有关。FOXP2的中断会导致儿童言语失用，这是一种言语障碍，其特点是难以准确地对发声运动动作进行排序。作者表明，成年鸣禽体内FoxP2的干扰同样会扰乱鸟鸣，并将多巴胺能信号与鸣叫产生的干扰联系起来。
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. Disruption of FOXP2 cause Childhood Apraxia of Speech, a speech disorder marked by difficulties in accurately sequencing vocal motor actions. The authors show that disruption of FoxP2 in the adult songbird similarly disrupts birdsong and link dopaminergic signalling to disruptions in song production.
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影响因子：
16.2
作者：
Ali F;Otchy TM;Pehlevan C;Fantana AL;Burak Y;Ölveczky BP
通讯作者：
Ölveczky BP
影响因子：
11.2
作者：
ALBIN, RL;REINER, A;YOUNG, AB
通讯作者：
YOUNG, AB
DOI：
10.1126/science.aah6837
发表时间：
2016-12-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gadagkar V;Puzerey PA;Chen R;Baird-Daniel E;Farhang AR;Goldberg JH
通讯作者：
Goldberg JH
DOI：
10.1073/pnas.1611146114
发表时间：
2017-05-30
影响因子：
11.1
作者：
Budzillo, Agata;Duffy, Alison;Perkel, David J.
通讯作者：
Perkel, David J.
影响因子：
4.6
作者：
Chen YJ;Friedman BA;Ha C;Durinck S;Liu J;Rubenstein JL;Seshagiri S;Modrusan Z
通讯作者：
Modrusan Z