Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX, USA.
Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA.
Nat Commun. 2021 May 11;12(1):2617. doi: 10.1038/s41467-021-22918-2.
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.
转录因子 FoxP2 在基底神经节中丰富表达，其突变会损害人类和鸣禽的发声能力。基底神经节对于运动动作的选择和排序很重要，但控制习得发声准确排序的回路机制尚不清楚。在这里，我们表明 FoxP2 在基底神经节中的表达对于鸟鸣的流畅起始和终止以及成年期歌唱音节排序的维持至关重要。FoxP2 的敲低会使纹状体中的多巴胺受体在直接途径和间接途径中的表达失衡，表明多巴胺信号在调节发声运动排序中的作用。证实了这一预测，我们表明，在歌唱过程中，多巴胺的相位激活而不是抑制会驱动歌唱音节的重复，从而也损害了鸟鸣的流畅起始和终止。这些发现表明鸣禽中声音元素的不流畅重复具有离散的回路起源，这对言语障碍具有启示意义。
