Estrogens and Central Auditory Processing of Birdsong

描述（由申请人提供）：鸣禽代表了一个成熟的模型来研究声音交流和学习以及性类固醇对大脑和行为的影响。有趣的是，与感知、辨别和记忆歌曲有关的神经回路也表达了高水平的芳香酶，这种酶与雌激素的前体睾酮合成有关。这种歌曲处理和雌激素生成元件之间的重叠发生在尾侧绒毛（NCM）中，这是一个中央听觉区域，与哺乳动物的听觉皮层的一部分相当。芳香化酶在NCM中富集表达的功能后果尚不清楚。本R21提案中的实验具有高度的探索性，旨在解决芳香化酶在NCM中表达的潜在作用的两个假设：1)我们假设雌激素通过芳香化酶的作用在NCM中循环和局部产生，调节鸣声处理电路的反应性，从而调节鸟类对听觉线索的反应，这些听觉线索对领土和生殖行为很重要。为了验证这一假设，我们将研究NCM中已知和新的歌曲诱导基因的表达水平是否受到雌激素的调节。2)我们假设NCM中歌唱反应神经元回路的激活调节了局部雌激素的产生，这可能对大脑生理和行为产生重要影响。为了验证这一假设，我们将直接测量鸣叫刺激的鸟类NCM中的芳香酶活性和雌激素水平。虽然很多关于鸣禽的研究都致力于听觉系统和性类固醇对大脑功能的影响，但这两个系统之间的潜在相互作用在很大程度上尚未被探索，特别是在像NCM这样的皮质样区域的水平上。因此，提出的实验与以前的研究有很大的不同，并将开辟新的研究途径。我们的努力可能会导致直接测量鸣禽大脑局部雌激素水平的方法的改进，以及雌激素调节的新基因靶点的潜在鉴定。研究结果将对理解环境和激素因素如何相互作用来调节鸟类和包括人类在内的其他脊椎动物的社会和生殖行为具有重要意义。尽管许多关于鸣禽的研究致力于听觉系统和性类固醇对脑功能的影响，但这两个系统之间的潜在相互作用在很大程度上尚未被探索，特别是在像NCM这样的皮质样区域的水平上。因此，提出的实验与以前的研究有很大的不同，并将开辟新的研究途径。研究结果将对理解环境和激素因素如何相互作用来调节鸟类和包括人类在内的其他脊椎动物的社会和生殖行为具有重要意义。

DESCRIPTION (provided by applicant): Songbirds represent a well-established model to study vocal communication and learning and the effects of sex steroids on brain and behavior. Intriguingly, the neuronal circuitry involved in the perception, discrimination and memorization of song also expresses high levels of aromatase, an enzyme involved in the synthesis of estrogen from its precursor testosterone. This overlap between song-processing and estrogen-generating elements occurs within the caudomedial nidopallium (NCM), a central auditory area comparable to a portion of the auditory cortex of mammals. The functional consequences of the enriched expression of aromatase in NCM are unknown. The experiments in this R21 proposal are highly exploratory in nature and are designed to address two hypotheses regarding the potential role of aromatase expression in NCM: 1) We hypothesize that estrogen, both circulating, and produced locally in NCM through the action of aromatase, modulates the responsiveness of song-processing circuitry, thereby regulating the bird's response to auditory cues important for territorial and reproductive behaviors. To test this hypothesis, we will examine whether the expression levels of known and novel song-induced genes in NCM are modulated by estrogen. 2) We hypothesize that the activation of song-responsive neuronal circuitry in NCM regulates the local production of estrogen, which could have important consequences for brain physiology and behavior. To test this hypothesis, we will conduct direct measurements of aromatase activity and estrogen levels in the NCM of song-stimulated birds. Although much research in songbirds has been dedicated to the auditory system and the effects of sex steroids on brain function, potential interactions between these two systems have been largely unexplored, particularly at the level of a cortical-like area like NCM. The experiments proposed are therefore a significant departure from previous studies and will open up new avenues of investigation. Our efforts are likely to result in an improved method for directly measuring local estrogen levels in the songbird brain, as well as the potential identification of novel gene targets of estrogen regulation. The results will be highly relevant to understanding how environmental and hormonal factors interact to regulate social and reproductive behaviors in birds and other vertebrates including humans. PUBLIC HEALTH RELEVANCE Although much research in songbirds has been dedicated to the auditory system and the effects of sex steroids on brain function, potential interactions between these two systems have been largely unexplored, particularly at the level of a cortical-like area like NCM. The experiments proposed are therefore a significant departure from previous studies and will open up new avenues of investigation. The results will be highly relevant to understanding how environmental and hormonal factors interact to regulate social and reproductive behaviors in birds and other vertebrates including humans.