Behavior-Linked FoxP2 Regulation Enables Zebra Finch Vocal Learning
Behavior-Linked FoxP2 Regulation Enables Zebra Finch Vocal Learning
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DOI：
10.1523/jneurosci.3715-14.2015
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发表时间：
2015-02-18
影响因子：
5.3
通讯作者：
White, Stephanie A.
中科院分区：
文献类型：
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作者：
Heston, Jonathan B.;White, Stephanie A.
FOXP2转录因子的突变导致遗传性言语和语言障碍，但FoxP2如何有助于学习这些声音交流信号仍不清楚。FoxP2在人类和鸣禽大脑的皮质纹状体回路中富集。实验击倒这种丰富的歌曲控制神经元的斑胸草雀基底神经节损害导师的歌曲模仿，表明足够的FoxP2水平是必要的正常的声乐学习。在未被操纵的鸟类中，发声练习急剧下调FoxP2，导致声音变异性增加和FoxP2靶基因的动态调节。为了确定这种行为调节是否对歌曲学习很重要，在这里，我们使用病毒驱动的FoxP2过表达来抵消其下调。这种操纵破坏了歌曲练习对声音变化的急性影响，并导致不准确的歌曲模仿。总之，这些发现表明，FoxP2的动态行为相关调节，而不是绝对水平，对声乐学习至关重要。
Mutations in the FOXP2 transcription factor cause an inherited speech and language disorder, but how FoxP2 contributes to learning of these vocal communication signals remains unclear. FoxP2 is enriched in corticostriatal circuits of both human and songbird brains. Experimental knockdown of this enrichment in song control neurons of the zebra finch basal ganglia impairs tutor song imitation, indicating that adequate FoxP2 levels are necessary for normal vocal learning. In unmanipulated birds, vocal practice acutely downregulates FoxP2, leading to increased vocal variability and dynamic regulation of FoxP2 target genes. To determine whether this behavioral regulation is important for song learning, here, we used viral-driven overexpression of FoxP2 to counteract its downregulation. This manipulation disrupted the acute effects of song practice on vocal variability and caused inaccurate song imitation. Together, these findings indicate that dynamic behavior-linked regulation of FoxP2, rather than absolute levels, is critical for vocal learning.