Auditory Protein Regulation in Normal & Abnormal States

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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.