Heston Jonathan B, White Stephanie A
Interdepartmental Program in Neuroscience, and Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California 90095.
Interdepartmental Program in Neuroscience, and Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California 90095
J Neurosci. 2015 Feb 18;35(7):2885-94. doi: 10.1523/JNEUROSCI.3715-14.2015.
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.
FOXP2转录因子的突变会导致一种遗传性的言语和语言障碍，但FoxP2如何促进对这些声音交流信号的学习仍不清楚。FoxP2在人类和鸣禽大脑的皮质纹状体回路中含量丰富。在斑胸草雀基底神经节的歌声控制神经元中，通过实验降低这种含量会损害对导师歌声的模仿，这表明正常的发声学习需要足够的FoxP2水平。在未进行操作的鸟类中，发声练习会使FoxP2急性下调，导致声音变异性增加以及对FoxP2靶基因的动态调节。为了确定这种行为调节对歌声学习是否重要，我们在此使用病毒驱动的FoxP2过表达来抵消其下调。这种操作破坏了发声练习对声音变异性的急性影响，并导致歌声模仿不准确。这些发现共同表明，与行为相关的FoxP2动态调节而非绝对水平对发声学习至关重要。
