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

FoxP2 在神经可塑性中的作用促进成人声乐学习和社交智力

基本信息

批准号：
8795049
负责人：
TIMOTHY F WRIGHT
金额：
$ 24.97万
依托单位：
NEW MEXICO STATE UNIVERSITY LAS CRUCES
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-15 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8795049
关键词：
Address Adolescent Adult Affect Animal Model Biomedical Research Birds Brain Child Childhood Cochlear Implants Cognitive Communication Complex Corpus striatum structure Defect Development Effectiveness Family Psittacidae Female Funding Gene Expression Gene Structure Genes Genetic Genetic Transcription Human Immigrant Knowledge Language Language Development Learning Life Measures Mediating Melopsittacus Minority-Serving Institution Modeling Morphology Mutation Neuroanatomy Neurobiology Neuronal Plasticity Neurons Neurosciences Pathway Analysis Pattern Perception Phase Play Postdoctoral Fellow Process Production Relative (related person)Research Research Training Role Shapes Social Behavior Songbirds Speech Speech Disorders Staging Stereotyping Stroke Structural defect Students Sum Techniques Testing Training United States National Institutes of Health Viral Vector Vocabulary Weight Work adeno-associated viral vector base cell type cognitive ability critical period density experience gene therapy insight male neurogenetics neuromechanism novel overexpression preference programs public health relevance relating to nervous system research study response sex social social communication social group social integration sound transcription factor transcriptome sequencing vocal learning vocalization zebra finch

项目摘要

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.

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一个核心方面，语言的一个关键神经过程是声音学习，即在大多数人学习其主要语言时学习构成语言的特定声音组合的能力。儿童时期确实会学习一门新语言，特别是对于外国出生的移民，以及人工耳蜗植入者和中风患者来说，但人们对成人大脑如何学习语言的突变知之甚少。转录因子众所周知，FoxP2 会导致人类语言缺陷。斑胸草雀（一种用于发声学习的鸣禽模型）的研究表明，转录因子 FoxP2 在调节构成神经中枢的其他基因方面在幼年阶段发挥着重要作用。重要的是，斑胸草雀只能在幼年时进行学习，这限制了其作为成年声音学习模型的有效性。在这个 SC1 项目中，我们将采用另一种模型，虎皮鹦鹉（一个小鹦鹉）在成年后通常会学习新的叫声，我们将使用该模型来研究 FoxP2 在成人发声学习中的作用，我们将使用为基因治疗开发的病毒载体来增加 FoxP2 在特定发声学习中的基因表达。然后，我们将检查对声音可塑性、社会行为、神经形状和基因表达网络的影响，我们预测 FoxP2 活性的升高将抑制声音可塑性，并降低或完全阻止接受治疗的鸟类学习新事物的能力。来自少数族裔服务机构的学生和博士后实习生将参与该研究的各个方面，并将接受一组经验丰富的合作者提供的神经科学尖端技术的培训。