Robust sex differences in brain and behavior exist in zebra finches. Only males sing, and critical forebrain regions are more developed in males. Factors driving these differences are not clear, but estradiol (E2) in female hatchlings partially masculinizes brain and behavior. Increased expression of Z-chromosome genes in males (ZZ; females: ZW) might contribute, perhaps by modifying neural responses to E2. Tubulin specific chaperone A (TBCA) is increased in the lateral magnocellular nucleus of the anterior nidopallium (LMAN) of juvenile males; these TBCA+ cells project to the robust nucleus of the archistriatum (RA). TBCA siRNA was unilaterally delivered to the LMAN of developing females treated with E2 and males treated with the aromatase inhibitor, fadrozole; the contralateral side of each animal received a control. Western blots confirmed average protein decreases of 59% (females) to 71% (males), and efficacy was validated in experimental animals with immunohistochemistry. In both males and females, siRNA treatment decreased TBCA+ cell number (F > 8.23, p ≤ 0.012). TBCA siRNA significantly decreased the volume of RA in both males and females (F > 13.01, p ≤ 0.002) and of LMAN in females (F = 5.32, p = 0.037). The volume of LMAN was increased in fadrozole treated compared to control males (F = 8.67, p = 0.009). RA cell size in both sexes was decreased by TBCA siRNA (F > 16.97, p ≤ .001), and within males, fadrozole increased RA cell size (F = 5.290, p = 0.034). TBCA siRNA also decreased total cell number in the RA of both sexes (F >10.78, p ≤ .005). These results suggest that TBCA is involved in masculinizing several song system features. As no significant interactions between the siRNA and hormone manipulations were detected, it appears that TBCA does not modulate the effects of E2.
Supported by NIH R01-MH096705