Teramitsu Ikuko, White Stephanie A
Interdepartmental Programs in Molecular, Cellular, and Integrative Physiology, University of California, Los Angeles, Los Angeles, California 90095, USA.
J Neurosci. 2006 Jul 12;26(28):7390-4. doi: 10.1523/JNEUROSCI.1662-06.2006.
Learned vocal communication, including human speech, is a socially influenced behavior limited to certain animals. This ability requires auditory feedback during vocalization, which allows for on-line evaluation, to achieve the desired vocal output. To date, FOXP2 (forkhead box P2), a transcriptional repressor, is the only molecule directly linked to human speech. Identified FOXP2 mutations cause orofacial dyspraxia accompanied by abnormalities in corticostriatal circuitry controlling voluntary orofacial movements. These observations implicate FOXP2 in the developmental formation of neural circuits used in speech, but whether FOXP2 additionally plays an active role in mature circuitry was unknown. To address this question, we use a songbird, the zebra finch (Taeniopygia guttata), whose learned song and underlying circuitry are well characterized. We show that, when adult males sing, FoxP2 mRNA is acutely downregulated within area X, the specific region of the songbird striatum dedicated to song. Furthermore, we find downregulation in males that sing by themselves (undirected singers) but not in males that sing to females (directed singers). This FoxP2 downregulation cannot be a simple consequence of the motor act because birds sang in both directed and undirected contexts. Our data suggest that FoxP2 is important not only for the formation but also for the function of vocal control circuitry. Social context-dependent, acute changes in FoxP2 within the basal ganglia of adult songbirds also suggest, by analogy, that the core deficits of affected humans extend beyond development and beyond basic central motor control.
习得性发声交流，包括人类语言，是一种受社会影响的行为，仅限于某些动物。这种能力在发声过程中需要听觉反馈，以便进行在线评估，从而实现所需的发声输出。迄今为止，转录抑制因子FOXP2（叉头框P2）是唯一与人类语言直接相关的分子。已发现的FOXP2突变会导致口面失用症，并伴有控制随意口面部运动的皮质纹状体回路异常。这些观察结果表明FOXP2参与了语言中使用的神经回路的发育形成，但FOXP2在成熟回路中是否还发挥积极作用尚不清楚。为了解决这个问题，我们使用了一种鸣禽——斑胸草雀（Taeniopygia guttata），其习得的歌声和潜在回路已得到充分表征。我们发现，成年雄性斑胸草雀唱歌时，FoxP2 mRNA在X区（鸣禽纹状体中专门用于唱歌的特定区域）内会急剧下调。此外，我们发现独自唱歌的雄性（无定向歌手）中FoxP2会下调，但向雌性唱歌的雄性（有定向歌手）中则不会。这种FoxP2的下调不可能仅仅是运动行为的简单结果，因为鸟类在有定向和无定向的情况下都会唱歌。我们的数据表明，FoxP2不仅对发声控制回路的形成很重要，而且对其功能也很重要。成年鸣禽基底神经节内FoxP2的社会背景依赖性急性变化也通过类比表明，受影响人类的核心缺陷不仅延伸到发育阶段，而且超出了基本的中枢运动控制。
