| Biological research relies heavily on animal models that enable direct physiological analyses. Each animal model is suitable to address different scientific questions. The songbird is a leading model for study of brain-behavior relationships, especially as a model for human speech. The strength of the songbird as a model lies in the rich complexity of singing behavior that is quantifiable and the identified neural circuitry which controls this learned behavior. Here, I study a songbird, zebra finch (Taeniopygia guttata ), as a model for vocal learning in order to unveil molecular mechanisms that are potentially shared between songbirds and humans.; My dissertation focuses on FoxP2, a transcriptional factor directly involved in human speech, for its role in birdsong. Mutations in FoxP2 are linked to severe speech and language disorders. Compellingly, I found that FoxP2 is expressed together with its heterodimerizing partner, FoxP1, in a striatal nucleus dedicated to song, Area X. Moreover, it is acutely down-regulated by the act of singing. This regulation is observed similarly in juveniles during song learning and in adults during song maintenance. Furthermore in adult birds, FoxP2 regulation depends on the social context of the behavior, occurring only when a male sings by itself and not when it directs its song to a female in the form of courtship. As a transcriptional factor, regulation of FoxP2 directly affects a cohort of downstream genes. Perhaps, reduced FoxP2 expression by singing regulates those genes to allow for plasticity to accommodate learning in juveniles and maintenance in adults.; To prove a function of a molecule, one should manipulate its expression and assess the outcome. For this, I developed a promising method of virus-mediated gene transfer and successfully manipulated 20∼30% of neurons in the vicinity of the injection site to alter expression of a fluorescent reporter gene and a functional transgene for a potassium channel. My work provides promising data on the ability to alter learned song in songbirds, and thereby make this model even stronger for study of brain-behavior relationships. Combined approaches of molecular and behavioral analyses will expand the understanding of physiological events orchestrated by legions of individual molecules. |
