NIH Director's Pioneer Award

需要解决的科学问题，以及为什么它很重要 我们建议解决的基本科学问题是确定基本神经和 发声学习的分子要求，口语的行为底物。语言是一种 使我们成为人类的基本行为。有了它，我们就能够交流复杂的概念，传递 文化上的知识，推进人类文明。由于脑损伤、创伤或 发育性疾病--我们生活在贫乏的社会交流和对他人的生活依赖中。 研究这一基本问题需要我们比较发声行为和相关的大脑通路。 在为数不多的几个有发声学习能力的群体中--四类远亲哺乳动物(人类、鲸类、 大象和蝙蝠)和三组远亲鸟类(鹦鹉、蜂鸟和鸣禽) 绝大多数没有这种基因的物种--非人类灵长类动物、啮齿动物、低音鸣禽、鸽子、 鸡等1、2.值得注意的是，尽管发声学习者彼此之间有遥远的亲缘关系，但那些大脑 已经研究过的鸟类(人类、鹦鹉、蜂鸟和鸣禽)，有证据表明它们有共同的 类似发声通路前脑组织：发声所必需的运动前或发声前通路(AVP) 学习，包括语法学习，以及产生语音所必需的运动或后发声通路(PVP 学习发音1。这些前脑通路在非发声学习者中是不存在的。然而，不会说话的人 似乎拥有类似的学习和产生非发声运动行为的大脑路径。考虑到这些 我们提出，有声学习者和非有声学习者之间的根本区别是一种基因 控制前脑运动学习通路连接的一个或几个遗传差异 通常控制先天发声产生的脑干运动神经元1。在这篇文章中，我概述了 以下是测试这一新想法的建议： 1.发现声乐学习者与非学习者在运动学习途径上的分子差异。 2.通过开发新的基因操作工具来操纵它们的网络连接性。 3.使用这些工具来改变发声核团的连通性，从而改变发声非学习者的发声行为， 潜在地允许其他物种修改和模仿声音，并允许纠正受损的声音 声乐学习者的发声学习脑通路。 在不学习发声的人中诱导这种连接和行为变化将会产生深远的影响 了解发声学习和语言进化的分子机制。正在修复 当声乐学习者的通路受损时，将对纠正神经功能障碍产生深远的影响 演讲。

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.