Sensory- and motor-driven genes in vocal communication

描述（由申请人提供）：本提案的目标是在正常和失聪受试者中识别由习得的声音交流激活的感觉和运动驱动基因。我们将使用的动物模型是一只鸣禽。鸣禽是唯一可接触的非人类动物之一，可以研究人类语言的基础——习得的声音交流。非人类灵长类动物、啮齿类动物和其他通常被研究的动物没有；这种能力。在鸣禽中，听到特定物种的发声（感觉活动）会引起整个听觉通路中基因表达的大量增加。这种感官驱动的表达是经验依赖的，因为诱导要求鸟类与成年同种动物一起饲养，当鸟类听到新的物种特异性歌曲时，诱导是最高的。这种表达被震耳欲聋所阻挡。产生模仿发声的行为（运动活动）在整个大脑发声通路中诱导基因表达的大量增加，并且这种运动驱动的表达不会被耳聋所阻断。然而，当鸟类像人类一样失聪时，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，需要基底神经节皮质样的发声途径，在该途径中发现了发声驱动基因表达。迄今为止，很少有基因被确定在行为过程中与这种感觉和运动驱动的调节有关，而且还没有一个基因被确定与耳聋引起的习得发声的退化有关。人们认为，在这些行为过程中，一个完整的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正常发声交流和耳聋导致的习得发声退化所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具有显著的同源性，我们的实验将使我们能够在鸣禽系统中识别具有人类/哺乳动物同源性的鸟类脑基因。

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.