Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA 90095.
eNeuro. 2019 Apr 15;6(2). doi: 10.1523/ENEURO.0071-19.2019. eCollection 2019 Mar-Apr.
In humans, mutations in the transcription factor forkhead box P2 (FOXP2) result in language disorders associated with altered striatal structure. Like speech, birdsong is learned through social interactions during maturational critical periods, and it relies on auditory feedback during initial learning and on-going maintenance. Hearing loss causes learned vocalizations to deteriorate in adult humans and songbirds. In the adult songbird brain, most FoxP2-enriched regions (e.g., cortex, thalamus) show a static expression level, but in the striatal song control nucleus, area X, FoxP2 is regulated by singing and social context: when juveniles and adults sing alone, its levels drop, and songs are more variable. When males sing to females, FoxP2 levels remain high, and songs are relatively stable: this "on-line" regulation implicates FoxP2 in ongoing vocal processes, but its role in the auditory-based maintenance of learned vocalization has not been examined. To test this, we overexpressed FoxP2 in both hearing and deafened adult zebra finches and assessed effects on song sung alone versus songs directed to females. In intact birds singing alone, no changes were detected between songs of males expressing FoxP2 or a GFP construct in area X, consistent with the marked stability of mature song in this species. In contrast, songs of males overexpressing FoxP2 became more variable and were less preferable to females, unlike responses to songs of GFP-expressing control males. In deafened birds, song deteriorated more rapidly following FoxP2 overexpression relative to GFP controls. Together, these experiments suggest that behavior-driven FoxP2 expression and auditory feedback interact to precisely maintain learned vocalizations.
在人类中，转录因子叉头框 P2（FOXP2）的突变导致与纹状体结构改变相关的语言障碍。与语言一样，鸟类鸣叫也是通过成熟关键期的社会互动学习而来的，它依赖于初始学习和持续维持期间的听觉反馈。听力损失会导致成年人类和鸣禽的习得性发声恶化。在成年鸣禽大脑中，大多数富含 FoxP2 的区域（例如皮层、丘脑）表现出静态表达水平，但在纹状体歌唱控制核区 X 中，FoxP2 受歌唱和社会环境的调节：当幼鸟和成年鸟独自歌唱时，其水平下降，歌曲变得更加多变。当雄性向雌性歌唱时，FoxP2 水平保持较高，歌曲相对稳定：这种“在线”调节暗示 FoxP2 参与了正在进行的发声过程，但它在听觉维持习得发声方面的作用尚未被检验。为了检验这一点，我们在听力正常和耳聋的成年斑马雀中过表达 FoxP2，并评估其对独自歌唱和向雌性歌唱的歌曲的影响。在完整鸟类独自歌唱时，表达 FoxP2 或 GFP 构建体的雄性在 X 区的歌曲之间没有检测到变化，与该物种成熟歌曲的显著稳定性一致。相比之下，过表达 FoxP2 的雄性的歌曲变得更加多变，对雌性的吸引力降低，这与 GFP 表达对照雄性歌曲的反应不同。在耳聋鸟类中，FoxP2 过表达后歌曲恶化得更快，与 GFP 对照相比。总的来说，这些实验表明，行为驱动的 FoxP2 表达和听觉反馈相互作用，精确地维持习得的发声。
