Estrogen and sex-dependent loss of the vocal learning system in female zebra finches

• Published in: Hormones and behavior 2021-03, Vol.129, p.104911-104911, Article 104911
• Main Authors: Choe, Ha Na, Tewari, Jeevan, Zhu, Kevin W., Davenport, Matthew, Matsunami, Hiroaki, Jarvis, Erich D.
• Format: Article
• Language: English
• Subjects: Animals; Aromatase inhibitor; Birdsong; Brain; Development; Estrogens - pharmacology; Exemestane; Female; Finches; Juvenile; Learning; Male; Plumage; Sex hormones; Specialized gene expression; Transcriptomics; Vocalization, Animal
• ISSN: 0018-506X; 1095-6867
• DOI: 10.1016/j.yhbeh.2020.104911

Sex hormones alter the organization of the brain during early development and coordinate various behaviors throughout life. In zebra finches, song learning is limited to males, with the associated song learning brain pathways only maturing in males and atrophying in females. While this atrophy can be prevented by treating females with exogenous estrogen during early post-hatch development, the requirement of estrogen during normal male song system development is uncertain. For the first time in songbirds, we administered exemestane, a potent third generation estrogen synthesis inhibitor, from the day of hatching until adulthood in order to reassess the role of estrogen in song circuit development. We examined the behavior, brain anatomy, and transcriptomes of individual song nuclei in these pharmacologically manipulated animals. We found that males with long-term exemestane treatment had diminished male-specific plumage and impaired song learning, but minimal effect on song nuclei sizes and their specialized transcriptome. Consistent with prior findings, females with long-term estrogen treatment retained a functional song system with song nuclei that had specialized gene expression similar, but not identical to males. We also observed that different song nuclei responded to estrogen manipulation differently, with Area X in the striatum being the most altered by estrogen modulation. These findings support the hypothesis that song learning is an ancestral trait in both sexes that was subsequently suppressed in females of some species and that estrogen has come to play a critical role in modulating this suppression as well as refinement of song learning. •First study using exemestane, a more potent 3rd generation aromatase inhibitor, in songbirds.•Found an unexpected relationship between estrogen and male plumage development in zebra finches.•Long-term inhibition of estrogen synthesis led to impaired song learning, but did not prevent it or the development of the song system.•Confirmed that delivery of large doses of estrogen prevented suppression of the female song system and song learning.•Song nuclei transcriptomes are similar, but not identical, between sexes and are impacted differently by estrogen.