Retinoid Signaling in Songbirds: Learned Song, Gene Expression and Neurogenesis

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DESCRIPTION (provided by applicant): Retinoid signaling is important in the development and maintenance of neuronal phenotypes. When disrupted in humans this results in learning disabilities. Work on vocal learning in song birds has identified the key brain centers responsible for the control and development of learned bird song, and proper retinoid signaling is one requirement for adequate function of these brain pathways. Songbirds learn their songs by listening to adult tutors, and perfect them through a period of trial and error- a process analogous to how humans learn language as children. This goal of this study is to elucidate how retinoid signaling specifically affects the avian song pathways. This will be achieved by two specific aims. The first aim is to measure the expression of genes known to be important in retinoid signaling and identify those that are expressed in the song pathway. Genes that show expression in the song system will be further characterized at the cellular level to identify the cell types and potential target areas of retinoid signaling in the brain. We will then use a synthetic diet paradigm to either supplement retinoic acid or remove all retinoic acid and its metabolic precursors from the diet to test how these genes, that are known to be retinoic responsive in other systems, respond to and regulate retinoid levels in the song centers. These results will seed a bio-informatics analysis of the retinoid signaling pathways that affect a complex learned behavior. Because neurogenesis and neuronal differentiation is a prominent trait that is regulated by retinoid signaling, aim two will test the effects that altered retinoid signaling has on rates of neuronal birth, migration and establishment within the song centers of the brain. PUBLIC HEALTH RELEVANCE Vitamin A deficiency is a major human health issue and has negative effects on cognitive development. Retinoids are also used therapeutically to treat acne and reduce the proliferation of promyelocytic leukemia, but with severe effects on human development. Rodent models are able to test effects on relational memory and spatial learning, but these species do not exhibit vocal learning as in humans. Songbirds such as the zebra finch do exhibit vocal learning and provide a suitable model to test the importance of retinoid signaling on speech development and learning disabilities.