NIH Director's Pioneer Award

NIH 院长先锋奖

基本信息

批准号：
7667950
负责人：
Erich D Jarvis
金额：
$ 76.17万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-30 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7667950
关键词：
Academic Medical Centers Acoustics Address Adult African American Age American Animal Behavior Animals Anterior Area Atrophic Auditory Award Bacillus (bacterium)Bacillus subtilis Basal Ganglia Behavior Behavioral Bioinformatics Biological Biological Assay Biology Biomedical Research Birds Brain Brain Injuries Brain Mapping Brain Stem Brain region Candidate Disease Gene Cell Nucleus Cells Centenarian Cerebrum Chemistry Chickens Chiroptera Chromosome Structures Ciliary Neurotrophic Factor Cities Civilization Clinical Research Collection Columbidae Communication Communication Research Complementary DNA Complex Computational Biology Corpus striatum structure Corticospinal Tracts DNA Sequence DNA Sequence Rearrangement Dancing Data Databases Dependency Development Disease Doctor of Philosophy Dorsal Ecology Education Educational Curriculum Elephants Embryo Engineering Evolution Face Faculty Failure Family Psittacidae Fellowship Figs - dietary Fortune Fostering Foundations Freedom Frequencies Funding Funding Mechanisms Gene Expression Gene Expression Profile Gene Expression Regulation Gene Transfer Genes Genetic Genetic Structures Genomics Glutamate Receptor Goals Grant Green Fluorescent Proteins Head Homologous Gene Human Husband Image Immediate-Early Genes Infection Injection of therapeutic agent Institutes International Internet Intranet Japanese Population Jordan Knowledge Language Language Disorders Laryngeal muscle structure Lead Learning Left Length Lentivirus Vector Lesion Libraries Life Link Literature Location Macaca Macaca mulatta Mammals Maps Mathematics Messenger RNA Methods Midbrain structure Minor Minority Modeling Modification Molecular Molecular Biology Molecular Neurobiology Motor Motor Neurons Motor Pathways Movement Muscle Music Mutation National Research Service Awards Nature Neural Pathways Neurites Neurobiology Neurons Neurosciences Neurotrophin 3 New York Nomenclature North Carolina Operative Surgical Procedures Organ Outcome Pan Genus Pathway interactions Pattern Peripheral Nerves Persons Plasmids Positioning Attribute Primates Process Production Promoter Regions Prosencephalon Proteomics Quail Rattus Recombinant adeno-associated virus (rAAV)Research Research Personnel Research Support Resources Risk Rodent Scholarship Schools Science Scientist Screening procedure Semantics Sensory Signal Transduction Sleep Social Environment Societies Songbirds Speech Spinal Cord Lesions Spinal cord injury Staging Structure Subfamily lentivirinae Synapses Syringes System Telencephalon Testing Time Tracer Traineeship Transduction Gene Trauma Troglodytinae United States National Institutes of Health Universities Viral Viral Vector Voice Woman Work adenovirus mediated delivery awake base bird song brain pathway brain research cDNA Library career cell type cognitive neuroscience college comparative complex biological systems computer based statistical methods computerized tools design essays feeding frontier gene correction gene function gene synthesis high risk high school hindbrain hypoglossal nucleus in vivo inhibitor/antagonist insight interest large scale production men motor learning nervous system disorder neurotrophic factor nonhuman primate novel nucleus ambiguus performing art positional cloning pre-doctoral prevent professor programs promoter psychologic rRNA Genes rRNA Operon relating to nervous system repaired research study simulation social communication sound symposium syntax tool transcription factor vocal learning vocalization willingness zebra finch

项目摘要

Scientific problem to be addressed, and why it is important The fundamental scientific problem we propose to address is to determine the basic neural and molecular requirements for vocal learning, the behavioral substrate for spoken language. Language is one of the essential behaviors that make us human. With it, we are able to communicate complex concepts, pass on knowledge culturally, and advance human civilization. Without it ¿ due to brain damage, trauma, or developmental diseases - we live a life of impoverished social communication and life dependency on others. Studying this fundamental problem requires that we compare the vocal behavior and associated brain pathways of the few rare groups that have vocal learning - four groups of distantly related mammals (humans, cetaceans, elephants, and bats) and three groups of distantly related birds (parrots, hummingbirds, and songbirds) ¿ with the vast majority of species that do not have it - non-human primates, rodents, suboscine songbirds, pigeons, chickens, etc.1,2. Remarkably, although vocal learners are distantly related to each other, of those whose brains that have been studied (humans, parrots, hummingbirds, and songbirds), evidence suggests that they share a similar vocal pathway forebrain organization: a premotor or anterior vocal pathway (AVP) necessary for vocal learning, including syntax learning, and a motor or posterior vocal pathway (PVP) necessary for production of learned vocalizations1. These forebrain pathways are not found in vocal non-learners. Yet, vocal non-learners appear to possess similar brain pathways for learning and production of non-vocal motor behaviors. Given these findings, we have proposed that the fundamental difference between vocal learners and non-learners is a genetic difference or several genetic differences that control the connection of forebrain motor learning pathways onto brainstem motor neurons that normally control the production of innate vocalizations1. In this essay, I outline the following proposal for testing this novel idea: 1. Discover molecular differences in the motor learning pathways between vocal learners and non-learners. 2. Manipulate their network connectivity by developing novel gene manipulation tools. 3. Use these tools to modify vocal nuclei connectivity and thus vocal behavior of a vocal non-learner, potentially allowing other species to modify and imitate sounds and allowing correction of damaged vocal learning brain pathways in vocal learners. Inducing such connectivity and behavioral changes in vocal non-learners would have profound impact towards understanding molecular mechanisms of vocal learning and evolution of language. Repairing the pathway in vocal learners, when damaged, would have profound impact for correcting neurological disorders of speech.

要解决的科学问题，以及为什么很重要我们建议解决的基本科学问题是确定基本神经和人声学习的分子要求，这是口语的行为底物。语言是使我们成为人类的基本行为。有了它，我们能够传达复杂的概念，传递在文化上知识，并推进人类文明。没有脑损伤，创伤或发展性疾病 - 我们过着贫穷的社会交流和对他人生活的依赖的生活。研究这个基本问题需要我们比较声音行为和相关的大脑途径在少数具有声音学习的稀有群体中，四组与明显相关的哺乳动物（人类，鲸类，，大象和蝙蝠）和三组遥远的鸟类（鹦鹉，蜂鸟和歌手）与没有它的绝大多数物种 - 非人类灵长类动物，啮齿动物，副岛歌手，鸽子，鸡等。1,2。值得注意的是，尽管声乐学习者彼此之间有着遥远的联系，但大脑已经研究了（人类，鹦鹉，蜂鸟和歌手），证据表明他们共享类似的人声途径前脑组织：声音所需的前声音或前声道（AVP）学习，包括语法学习，以及生产所需的电动机或后声通路（PVP）学习的声音1。这些前脑途径在人声非学习者中找不到。但是，人声非学习者似乎有可能用于学习和生产非声音运动行为的类似大脑途径。鉴于这些调查结果，我们提出，人声学习者和非学习者之间的基本差异是一种遗传差异或几种遗传差异控制着前脑运动学习途径的连接通常控制先天发声的产生的脑干运动神经元1。在本文中，我概述了测试这一新颖想法的以下建议： 1。发现声乐学习者和非学习者之间运动学习途径的分子差异。 2。通过开发新型基因操纵工具来操纵其网络连接。 3。使用这些工具来修改声带核连接性，从而改变人声非学习者的声音行为，可能允许其他物种修改和模仿声音并允许校正受损声带学习人的大脑道路。引起人声非学习者的这种连通性和行为变化将产生深远的影响要了解语音学习和语言演变的分子机制。修理声带学习者的途径，如果受损，将对纠正神经系统疾病产生深远影响演讲。