The long-term objectives of this research are to understand how hormones and coactivators act on the brain within a critical window in development to create sex differences in vocal learning and production.  The study will elucidate how coactivators are able to increase sensitivity of steroid receptors.  Specifically, to identify how low levels of hormones may be important in producing drastic and long-lasting effects on the organism.  The Australian zebra finch (ZF; Taeniopygia guttata) serves as a powerful model system since males show a robust sex difference in song production and behavior and song nuclei morphology.  These sex differences appear to be hormonally mediated however, hormonal manipulations of estradiol and/or testosterone are unable to cause the naturally occuring effect.  This study aims to test our hypothesis that the coactivator, L7 Switch Protein for the Antagonist (L7/SPA) mediates these differences.  The specific aims of this study are: SA 1: Test whether L7/SPA interacts with estradiol and it's receptor ER-?  in neurons of the song nuclei.  SA 2: Test whether decreasing L7/SPA protein levels in the developing male ZF brain alters neuronal proliferation (in vivo) and sexual differentiation and song production (in vitro).  The use of the ZF as a model for studying sexual differentiation of the song control nuclei will further enhance our understanding of how coactivators, such as L7/SPA, are working to mediate sex differences in the brain and behavior and the plasticity of the brain.  By understanding the mechanisms that control these sex differences, we will be better able to identify the mechanisms underlying the development of vocal learning and production. [ unreadable] [unreadable] [unreadable]