Auditory Protein Regulation in Normal & Abnormal States

正常情况下的听觉蛋白质调节

基本信息

批准号：
7254135
负责人：
Erich D Jarvis
金额：
$ 18.93万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7254135
关键词：
Adult Animals Auditory Basal Ganglia Behavior Behavioral Biological Models Birds Brain Cell Nucleus Cerebrum Communication Condition Control Groups Deterioration Development Disease Elderly Excision Future Gel Gene Expression Gene Proteins Genes Genetic Goals Hearing Hearing Impaired Persons Homologous Gene Human Label Language Learning Maintenance Mass Spectrum Analysis Monitor Motor Neuraxis Pathway interactions Population Prevention Process Production Proteins Proteomics Regulation Regulator Genes Resources Rodent Role Sensory Sensory Process Songbirds Speech Staging System Testing Thalamic structure Thinking Time Writing auditory feedback auditory pathway brain pathway gel electrophoresis hearing impairment male nonhuman primate prevent protein expression research study response sound two-dimensional vocal learning vocalization zebra finch

Adult Animals Auditory Basal Ganglia Behavior Behavioral Biological Models Birds Brain Cell Nucleus Cerebrum Communication Condition Control Groups Deterioration Development Disease Elderly Excision Future Gel Gene Expression Gene Proteins Genes Genetic Goals Hearing Hearing Impaired Persons Homologous Gene Human Label Language Learning Maintenance Mass Spectrum Analysis Monitor Motor Neuraxis Pathway interactions Population Prevention Process Production Proteins Proteomics Regulation Regulator Genes Resources Rodent Role Sensory Sensory Process Songbirds Speech Staging System Testing Thalamic structure Thinking Time Writing auditory feedback auditory pathway brain pathway gel electrophoresis hearing impairment male nonhuman primate prevent protein expression research study response sound two-dimensional vocal learning vocalization zebra finch

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项目摘要

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％的美国人口聋，65岁的人口大约有29.1％的听力损失问题。这些问题在学习的语音中导致恶化。该提案的目的是使用鸣禽作为模型系统鉴定参与学习发声的主动恶化的蛋白质。鸣禽是唯一可以研究唯一可访问的非人类动物的动物之一，可以研究学习的声带交流，即人类语言的基材。其他经常研究的动物没有这种能力。在鸣禽中，听到自己发声会引起听觉途径部分的基因和蛋白质表达的大量增加。该表达式被震耳欲聋的阻塞。发声的行为还引起了声音途径中的基因和蛋白质表达的大量增加。当鸟类像人类一样聋时，他们学到的发声会恶化。鸣禽中的这种恶化是一个活跃的过程，涉及声途径的基底神经神经皮质状的一部分，其中发现了声音化的基因表达。也就是说，预防完整动物的恶化要求他们听到自己的声音反馈发声。迄今为止，很少有这种感觉和运动驱动调节的蛋白质被鉴定出来，并且没有发现随着聋哑诱导的学习发声的恶化而变化。据信，在这些行为过程中激活了整个基因调节网络。我们将使用行为，神经解剖学和高吞吐量蛋白质组学方法来识别和表征通过正常听到自己的声音作为对照组而激活的蛋白质，并通过聋哑诱发的诱导的降解对学到的发声作为实验组。由于大多数鸣鸟蛋白与已知的哺乳动物蛋白具有重要的同源性，因此我们的实验将使我们能够鉴定出具有人类同源物在Songbird System中具有实验表征的人类同源物。我们的长期目标是操纵这种蛋白质，以防止聋哑引起的声音恶化。