Auditory Protein Regulation in Normal & Abnormal States

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岁以上的人有听力损失问题。这些问题会导致语言学习能力下降。这项建议的目标是确定蛋白质参与主动恶化的学习发声，鸣禽作为一个模型系统。鸣禽是唯一一种可以研究人类语言基础的非人类动物。其他研究的动物没有这种能力。在鸣禽中，听到自己的声音会诱导听觉通路部分基因和蛋白质表达的大量增加。表情被震耳欲聋挡住了。发声的行为也诱导发声通路中基因和蛋白质表达的大量增加。当鸟类像人类一样被激怒时，它们习得的发声能力就会退化。鸣禽的退化是一个主动过程，涉及发声通路的基底神经节皮质样部分，在该部分发现了发声驱动的基因表达，也就是说，防止完好动物的退化需要它们通过听觉反馈听到自己的发声。到目前为止，很少有蛋白质已被确定与这种感觉和电机驱动的调节，并没有被确定的变化与中毒引起的恶化学习发声。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的方法，以确定和表征蛋白质激活正常的听力自己发声作为对照组，并作为实验组的学习发声的退化。由于大多数鸣禽蛋白质具有显着的同源性，已知的哺乳动物蛋白质，我们的实验将使我们能够确定鸟类的大脑蛋白与人类的同源物服从鸣禽系统的实验表征。我们的长期目标是操纵这些蛋白质，以防止过敏引起的声音退化。

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.