Role of FoxP2 in neural plasticity subserving adult vocal learning and social int

 描述(由申请人提供)：通过语言进行复杂的社交交流是人类互动的核心方面。语言背后的一个关键神经过程是语音学习，即学习构成语言的特定声音组合的能力。虽然大多数人在孩提时代就学习他们的母语(S)，但成年后确实会学习一门新的语言，特别是外国出生的移民，但接受人工耳蜗术的人和中风患者也是如此。然而，人们对成人大脑如何学习语言知之甚少。已知转录因子FoxP2的突变是人类语音缺陷的原因。对斑马雀的研究表明，转录因子FoxP2在幼年阶段发挥着重要作用，调节其他基因，这些基因构成了声音学习的神经中心，并增强了学习所需的神经连接。斑马雀是一种用于声音学习的鸣禽模型。重要的是，斑马雀只能在青少年时期学习，这限制了它作为成人发声学习模型的有效性。在这个SC1项目中，我们将使用另一个模型，虎皮鹦鹉(一种小鹦鹉)，它通常在成年后学习新的叫声。我们将利用这个模型来研究FoxP2在成人发声学习中的作用。我们将使用一种用于基因治疗的病毒载体来增加虎皮鹦鹉特定发声学习中心中FoxP2的基因表达。然后，我们将研究由此产生的对声音可塑性、社会行为、神经元形状和基因表达网络的影响。我们预测，FoxP2活性的升高将抑制发声的可塑性，并降低或完全阻断接受治疗的鸟类学习新发声的能力。来自少数族裔服务机构的学生和博士后实习生将参与研究的所有方面，并将从一群经验丰富的合作者那里接受神经科学尖端技术的培训。

 DESCRIPTION (provided by applicant): Complex social communication via language is a central aspect of human interactions. A key neural process underlying language is vocal learning, the ability to learn the particular sound combinations that compose a language. While most people learn their primary language(s) as children, learning of a new language as an adult does occur, particularly by foreign-born immigrants but also by recipients of cochlear implants and by stroke victims. Yet little is known about how the adult brain learns languages. Mutations in the transcription factor FoxP2 are known to be responsible for speech defects in humans. Work in the zebra finch, a songbird models for vocal learning, has suggested that the transcription factor FoxP2 plays an important role during the juvenile phase in regulating other genes that structure the neural centers for vocal learning and enhance the neural connections required for learning. Importantly, the zebra finch is capable of learning only as a juvenile, limiting its effectiveness as a model for adult vocal learning. In this SC1 project we will employ an alternative model, the budgerigar (a small parrot) that commonly learns new calls as an adult. We will use this model to investigate of the role of FoxP2 in adult vocal learning. We will use a viral vector developed for gene therapy to increase the gene expression of FoxP2 in a particular vocal learning center of budgerigars. We will then examine the resulting effects on vocal plasticity, social behavior, neuron shape and networks of gene expression. We predict that elevated FoxP2 activity will inhibit vocal plasticity and reduce or block completely the abiliy of treated birds to learn new vocalizations. Students and a postdoctoral trainee from a minority-serving institution will be involved in all aspects of the research and will receive training in cutting-edge techniques in neuroscience from a suite of highly-experienced collaborators.