Regulation of Neural Circuits Underlying Mammalian Reproduction

哺乳动物繁殖神经回路的调节

• 批准号: 1025893
• 负责人: Alexander Kauffman
• 金额: $ 90万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1025893&HistoricalAwards=false
• 关键词: Regulation; Neural; Circuits; Underlying; Mammalian

Kisspeptin, a recently-identified neuropeptide encoded by the Kiss1 gene, is both necessary and sufficient for puberty onset and adulthood fertility; however, exactly how Kiss1 neurons, which are known to be located in the hypothalamus, are themselves regulated is poorly understood. In females, Kiss1 neurons in the anterior hypothalamus are regulated by temporal signals from the brain?s circadian clock, thereby generating a precisely-timed activation of the reproductive axis that results in ovulation. Interestingly, this circadian regulation of Kiss1 neurons is fully dependent on the presence of the hormone estradiol, but how and where in the brain estradiol acts to induce the circadian activation of Kiss1 neurons is unknown. Additionally, the Kauffman lab has identified a novel extra-hypothalamic population of Kiss1 neurons in the amygdala which is also stimulated by estradiol; however, the molecular mechanisms of this regulation and the functions of amygdala Kiss1 neurons are completely unknown. Using mice, this research will ascertain the neuroanatomical location and molecular mechanism(s) by which hypothalamic Kiss1 neurons are regulated by both hormonal signals and circadian cues, and will also elucidate the hormonal regulatory mechanisms and potential functions of the novel Kiss1 population located in the amygdala. This intellectual merit of this research is a better understanding of how, when, and where in the brain hormones, particularly estradiol, regulate the function of critical pubertal and reproductive neural circuits, in particular, Kiss1 circuits. The research component is complimented and integrated with the outreach and broader impact aspects, which are to directly train and educate undergraduate and graduate students in hands-on biology research, to participate in the UCSD Initiative for Maximizing Student Diversity which engages and mentors undergraduate minority students in biology research, and to design and manage a new dynamic science website (Neuroendo Now) that serves as a public forum for, and disseminates current information pertaining to advances in neuroendocrinology.

Kisspeptin是最近发现的一种由Kiss 1基因编码的神经肽，对于青春期的开始和成年期的生育能力都是必要的，也是足够的;然而，Kiss 1神经元（已知位于下丘脑）本身是如何调节的却知之甚少。在女性中，下丘脑前部的Kiss 1神经元受来自大脑的时间信号调节。的生物钟，从而产生一个精确定时的激活生殖轴，导致排卵。有趣的是，这种Kiss 1神经元的昼夜节律调节完全依赖于激素雌二醇的存在，但雌二醇在大脑中如何以及在何处诱导Kiss 1神经元的昼夜节律激活尚不清楚。此外，Kauffman实验室已经在杏仁核中发现了一种新的下丘脑外Kiss 1神经元群体，它也受到雌二醇的刺激;然而，这种调节的分子机制和杏仁核Kiss 1神经元的功能完全未知。使用小鼠，本研究将确定下丘脑Kiss 1神经元受激素信号和昼夜节律线索调节的神经解剖学位置和分子机制，并将阐明位于杏仁核中的新型Kiss 1群体的激素调节机制和潜在功能。这项研究的智力价值是更好地了解大脑激素，特别是雌二醇，如何，何时和何地调节关键的青春期和生殖神经回路的功能，特别是Kiss 1回路。研究部分是互补的，并与外展和更广泛的影响方面，这是直接培训和教育本科生和研究生在动手生物学研究，参加UCSD倡议最大限度地提高学生多样性，从事和指导本科少数民族学生在生物学研究，并设计和管理一个新的动态科学网站（Neuroendo Now），作为一个公共论坛，并传播有关神经内分泌学进展的最新信息。