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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会交流是人类互动的一个核心方面。语言背后的一个关键神经过程是声音学习，即学习组成语言的特定声音组合的能力。虽然大多数人在儿童时期学习他们的主要语言，但成年后学习一门新语言的情况确实存在，特别是外国出生的移民，但也有人工耳蜗植入者和中风患者。然而，人们对成年人的大脑如何学习语言知之甚少。转录因子FoxP2的突变是人类语言缺陷的原因。对斑胸草雀（一种用于发声学习的鸣禽模型）的研究表明，转录因子FoxP2在幼年期在调节其他基因方面发挥着重要作用，这些基因构成了发声学习的神经中心，并增强了学习所需的神经连接。重要的是，斑胸草雀只能在幼年时学习，这限制了它作为成年人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（一种小鹦鹉）通常在成年后学习新的叫声。我们将使用这个模型来研究FoxP2在成人发声学习中的作用。我们将使用一种为基因治疗开发的病毒载体来增加FoxP2在虎皮鹦鹉特定发声学习中心的基因表达。然后，我们将研究对声音可塑性，社会行为，神经元形状和基因表达网络的影响。我们预测，FoxP2活性升高将抑制声音可塑性，并降低或完全阻断治疗的鸟类学习新的发声的能力。来自少数民族服务机构的学生和博士后实习生将参与研究的各个方面，并将从一群经验丰富的合作者那里接受神经科学前沿技术的培训。