Sensory- and motor-driven genes in vocal communication

描述(由申请人提供)：这项建议的目标是在正常和失聪的受试者中识别由习得的声音交流激活的感觉和运动驱动的基因。我们将使用的动物模型是一只鸣鸟。鸣禽是唯一可以研究人类语言基础--学习的声音交流的非人类动物之一。非人灵长类动物、啮齿动物和其他被普遍研究的动物不具备这种能力。在鸣禽中，听觉物种特有的发声(感官活动)会在整个听觉通路中诱导基因表达的大幅增加。这种感官驱动的表达依赖于经验，因为感应需要用成年同种鸟来饲养，当鸟听到新的物种特有的歌声时，感应最高。这个表情被震耳欲聋的声音挡住了。产生模仿发声的行为(运动活动)会导致大脑发声通路中基因表达的大幅增加，这种由运动驱动的表达不会被耳聋所阻止。然而，当鸟类像人类一样耳聋时，它们习得的发声能力就会恶化。在鸣禽中，这种退化是一个活跃的过程，需要基底节皮质样发声通路，在这个通路中发现了发声驱动的基因表达。到目前为止，很少有基因被识别出在行为过程中受到这种感觉和运动驱动的调节，也没有被识别出随着耳聋导致的习得发声恶化而发生变化的基因。人们认为，在这些行为过程中，整个基因调控网络被激活。我们将使用行为、神经解剖学和高通量分子生物学方法来识别和表征由正常发声交流和聋人导致的习得性发声恶化激活的感觉和运动驱动基因。由于大多数鸣禽基因与已知的哺乳动物基因有显着的同源性，我们的实验将使我们能够在鸣鸟系统中识别具有人类/哺乳动物同源基因的鸟类大脑基因。

DESCRIPTION (provided by applicant): The goal of this proposal is to identify sensory- and motor-driven genes activated by learned vocal communication in normal and deafened subjects. The animal model we will utilize is a songbird. Songbirds are one of the only accessible non-human animals where learned vocal communication, the substrate for human language, can be studied. Non-human primates, rodents, and other commonly studied animals do not have; this ability. In songbirds, hearing species-specific vocalizations (sensory activity) induces large increases of gene expression throughout the auditory pathway. This sensory-driven expression is experience-dependent, as induction requires that the birds be raised with adult conspecifics and induction is highest when the birds hear novel species-specific songs. The expression is blocked by deafening. The act of producing imitated vocalizations (motor activity) induces large increases of gene expression throughout the cerebral vocal pathway, and this motor-driven expression is not blocked by deafening. However, when birds are deafened, like humans, their learned vocalizations deteriorate. This deterioration, in songbirds, is an active process that requires the basal ganglia cortical-like vocal pathway, in which vocalizing-driven gene expression is found. To date, few genes have been identified with such sensory- and motor-driven regulation during behavior and none have yet 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 molecular biological approaches to identify and characterize sensory and motor-driven genes activated by normal vocal communication and by deafened-induced deterioration of learned vocalizations. Since most songbird genes have significant homology to known mammalian genes our experiments will enable us to identify avian brain genes with humain/mammalian homologues amenable to experimental characterization in the songbird system.