Auditory Protein Regulation in Normal & Abnormal States

正常情况下的听觉蛋白质调节

• 批准号: 7148247
• 负责人: Erich D Jarvis
• 金额: $ 23.33万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7148247
• 关键词: genes; hearing; human; learning; motivation; proteins; songbirds; vocalization

DESCRIPTION (provided by applicant): About 1% of the US population are deaf, and about 29.1% over the age of 65 have hearing loss problems. These problems cause deterioration in learned speech. The goal of this proposal is to identify proteins involved in active deterioration of learned vocalizations, using songbirds as a model system. Songbirds are one of the only accessible non-human animals where learned vocal communication, the substrate for human language, can be studied. Other commonly studied animals do not have this ability. In songbirds, hearing oneself vocalize induces large increases of gene and protein expression in parts of the auditory pathway. The expression is blocked by deafening. The act of vocalizing also induces large increases of gene and protein expression in the vocal pathway. When birds are deafened, like humans, their learned vocalizations deteriorate. This deterioration in songbirds is an active process involving the basal ganglia cortical-like part of the vocal pathway, in which vocalizing-driven gene expression is found. That is, the prevention of deterioration in intact animals requires that they hear themselves vocalize by auditory feedback. To date, few proteins have been identified with such sensory- and motor-driven regulation and none have been identified that change with deafening-induced deterioration of learned vocalizations. It is believed that an entire gene regulatory network is activated in these behavioral processes. We will use behavioral, neuroanatomical, and high throughput proteomic approaches to identify and characterize proteins activated by normal hearing of oneself vocalize as a control group and by deafened-induced deterioration of learned vocalizations as an experimental group. Since most songbird proteins have significant homology to known mammalian proteins, our experiments will enable us to identify avian brain proteins with human homologues amenable to experimental characterization in the songbird system. Our long-term goal is to manipulate such proteins to prevent deafened-induced vocal deterioration.

描述（由申请人提供）：大约 1% 的美国人口是聋人，大约 29.1% 的 65 岁以上老人有听力损失问题。这些问题会导致习得的言语能力下降。该提案的目标是使用鸣禽作为模型系统，识别参与习得发声主动退化的蛋白质。鸣禽是唯一可以研究习得的声音交流（人类语言的基础）的非人类动物之一。其他经常研究的动物不具备这种能力。在鸣禽中，听到自己发声会导致听觉通路部分基因和蛋白质表达大幅增加。表情被震耳欲聋的堵住了。发声行为还会引起发声通路中基因和蛋白质表达的大幅增加。当鸟类像人类一样失聪时，它们习得的发声能力就会减弱。鸣禽的这种退化是一个活跃的过程，涉及发声通路的基底神经节皮质样部分，其中发现了发声驱动的基因表达。也就是说，防止完整动物的恶化需要它们通过听觉反馈听到自己的声音。迄今为止，很少有蛋白质被发现具有这种感觉和运动驱动的调节作用，也没有发现任何蛋白质会随着震耳欲聋引起的习得发声恶化而改变。据信，整个基因调控网络在这些行为过程中被激活。我们将使用行为、神经解剖学和高通量蛋白质组学方法来识别和表征由自己发声的正常听力（作为对照组）和由耳聋引起的习得发声退化（作为实验组）激活的蛋白质。由于大多数鸣禽蛋白质与已知的哺乳动物蛋白质具有显着的同源性，因此我们的实验将使我们能够识别鸟类大脑蛋白质与人类同源物，这些蛋白质适合鸣禽系统中的实验表征。我们的长期目标是操纵这些蛋白质来防止耳聋引起的声音恶化。