Estrogens and Central Auditory Processing of Birdsong

描述（由申请人提供）：鸣禽是研究声音交流和学习以及性类固醇对大脑和行为影响的成熟模型。有趣的是，参与感知、辨别和记忆歌曲的神经元回路也表达高水平的芳香酶，这是一种参与从其前体睾酮合成雌激素的酶。这种歌声处理和雌激素产生元件之间的重叠发生在尾内侧巢皮质（NCM）内，这是一个中央听觉区域，相当于哺乳动物听觉皮层的一部分。NCM中芳香化酶的富集表达的功能后果是未知的。在这个R21提案中的实验本质上是高度探索性的，并且被设计来解决关于芳香酶表达在NCM中的潜在作用的两个假设：1）我们假设，通过芳香酶的作用，在NCM中循环和局部产生的雌激素调节歌曲处理电路的响应性，从而调节鸟对对于领土和生殖行为重要的听觉线索的响应。为了验证这一假设，我们将研究已知的和新的歌曲诱导的基因在NCM的表达水平是否受到雌激素的调节。2)我们推测，NCM中的歌曲响应神经元回路的激活调节了雌激素的局部产生，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，我们将进行直接测量的芳香化酶活性和雌激素水平的NCM的歌曲刺激的鸟类。虽然鸣禽的许多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探索，特别是在NCM等皮质样区域的水平上。因此，所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一种改进的方法，直接测量局部雌激素水平的鸣禽大脑，以及潜在的识别新的基因靶点的雌激素调节。这些结果将与理解环境和激素因素如何相互作用以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高度相关。公共卫生相关性虽然对鸣禽的研究主要集中在听觉系统和性类固醇对大脑功能的影响上，但这两个系统之间的潜在相互作用在很大程度上尚未探索，特别是在NCM等皮质样区域的水平上。因此，所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。这些结果将与理解环境和激素因素如何相互作用以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高度相关。

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.