No abstract

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, and the associated song learning brain pathway only matures in males and atrophies in females. This atrophy can be reversed by giving females exogenous estrogen during early post-hatch development, but whether normal male song system development requires estrogen 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. We examined the behavior, brain, and transcriptome of individual song nuclei of these pharmacologically manipulated animals. We found that males with long-term exemestane treatment had diminished male-specific plumage, impaired song learning, but retained normal song nuclei sizes and most, but not all, of their specialized transcriptome. Consistent with prior findings, females with long-term estrogen treatment retained a functional song system, and we further observed their song nuclei had specialized gene expression profiles 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, which 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.

No abstract

Zebra finches are sexually dimorphic vocal learners. Males learn to sing by imitating mature conspecifics, but females do not. The lack of vocal learning in females is associated with anatomical differences in the neural circuits responsible for vocal learning, including the atrophy of several brain regions during development1. However, this atrophy can be prevented and song learning retained in females after pharmacological estrogen treatment2–4. Little is known about the genetic machinery controlling this sex and estrogen responsive song system development. To screen for drivers, we performed an unbiased analysis of transcriptomes from song control nuclei and surrounding motor regions in zebra finches of either sex treated with 17-β-estradiol or vehicle until sacrifice on day 30, when divergence between the sexes is anatomically apparent. Utilizing the newly assembled autosomes and sex chromosomes from the zebra finch Vertebrate Genomes Project assemblies5, we identified correlated gene modules that were associated to song nuclei in a sex and estradiol dependent manner. Female estradiol treated HVC, in the vocal learning circuit, acquired the smallest of the modular specializations observed in male HVC. This module was enriched for genes governing anatomical development, and it’s specilization was dispraportionately influenced by the expression of Z sex chromosome transcripts in HVC. We propose that vocal learning may be prevented in female zebra finches via the suppression of an estrogen inducible Z chromosome cis-acting regulatory element.