Estrogens and Central Auditory Processing of Birdsong

雌激素与鸟鸣的中枢听觉处理

• 批准号: 7599287
• 负责人: Claudio V Mello
• 金额: $ 21.41万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7599287
• 关键词: Acoustic Stimulation; Address; Affect; Area; Aromatase; Auditory; Auditory area; Auditory system; Behavior; Birds; Brain; Communication; Complex; Comprehension; Condition; Coupled; Cues; Discrimination; Elements; Endocrine system; Enzymes; Estradiol; Estrogens; Exposure to; Gene Expression; Gene Targeting; Genes; Goals; Gonadal Steroid Hormones; Hearing; Hormonal; Human; Investigation; Language; Language Development; Learning; Learning Disabilities; Mammals; Measurement; Measures; Methods; Modeling; Nature; Neurons; Neurosecretory Systems; Pathway interactions; Pattern; Perception; Physiology; Process; Production; Property; Public Health; Regulation; Reproductive Behavior; Research; Role; Sex Behavior; Sex Characteristics; Shapes; Signal Transduction; Site; Social Controls; Songbirds; Speech; System; Telencephalon; Territoriality; Testing; Testosterone; Vertebrates; base; bird song; brain behavior; design; improved; neuronal circuitry; novel; programs; reproductive; research study; response; social; vocal learning

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.

描述（由申请人提供）：鸣禽代表了一种完善的模型，用于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，参与歌曲感知、辨别和记忆的神经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。歌曲处理元件和雌激素生成元件之间的这种重叠发生在尾内侧巢状皮质（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 中芳香酶丰富表达的功能后果尚不清楚。 R21 提案中的实验本质上是高度探索性的，旨在解决关于芳香酶表达在 NCM 中的潜在作用的两个假设：1）我们假设雌激素（在 NCM 中循环并通过芳香酶的作用在 NCM 中局部产生）调节歌曲处理电路的反应能力，从而调节鸟类对听觉线索的反应，这对领地和繁殖行为很重要。为了检验这一假设，我们将检查 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中歌曲反应神经元回路的激活调节雌激素的局部产生，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，我们将直接测量受鸣叫刺激的鸟类 NCM 中的芳香酶活性和雌激素水平。尽管对鸣禽的大量研究一直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 NCM 等类似皮质区域的水平上。因此，所提出的实验与以前的研究有很大不同，并将开辟新的研究途径。我们的努力可能会产生一种改进的方法，用于直接测量鸣禽大脑中的局部雌激素水平，以及潜在地鉴定雌激素调节的新基因靶标。这些结果将与了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。公共健康相关性 尽管对鸣禽的大量研究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 NCM 等类似皮质区域的水平上。因此，所提出的实验与以前的研究有很大不同，并将开辟新的研究途径。这些结果将与了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。