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Functional characterization of neural circuits controling puberty in female mice

控制雌性小鼠青春期的神经回路的功能特征

基本信息

批准号：
223107267
负责人：
Professor Dr. Ulrich Boehm
金额：
--
依托单位：
FR Experimentelle und Klinische Pharmakologie und Toxikologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2012
资助国家：
德国
起止时间：
2011-12-31 至 2016-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/223107267?language=en
关键词：
Functional characterization neural circuits controling

项目摘要

Puberty onset is initiated in the brain by activating gonadotropin-releasing hormone (GnRH) neurosecretion. Different permissive signals must be integrated for the initiation of reproductive maturation, however the neural circuits controlling timely awakening of the reproductive axis are not understood. The identification of the neuropeptide kisspeptin as a potent activator of GnRH neuronal activity has provided an opportunity for understanding how timing and progression of puberty are controlled. We have recently shown that two estrogen receptor α -dependent mechanisms – one acting like a “brake” and the other acting like an “accelerator” - are sequentially operated in kisspeptin-producing neurons during pubertal development of female mice to gate, and then to activate GnRH release. Our data suggest that the temporal coordination of juvenile restraint and subsequent pubertal activation are mediated by two separate neural circuits in the hypothalamus. We hypothesize that kisspeptin neurons in the arcuate nucleus (ARC) control puberty onset whereas kisspeptin neurons in the anteroventral periventricular nucleus (AVPe) control completion of puberty. The aim of this proposal is to test this hypothesis and analyze the functional role of ARC and AVPe neural circuits during puberty. We will analyze the neural circuitry of ARC and AVPe kisspeptin neurons using a genetic transneuronal tracing approach. Also we will investigate these circuits in living animals using optogenetic activation/inhibition of ARC and AVPe kisspeptin neurons, respectively, while monitoring the animal's endocrine state.

通过激活促性腺激素释放激素（GnRH）神经分泌在大脑中启动青春期发作。不同的许可信号必须整合生殖成熟的启动，但控制生殖轴的及时唤醒的神经回路还不清楚。神经肽kisspeptin作为GnRH神经元活性的有效激活剂的鉴定为了解青春期的时间和进展是如何控制的提供了机会。我们最近发现，在雌性小鼠青春期发育过程中，两种雌激素受体α依赖性机制--一种像“刹车”，另一种像“加速器”--在kisspeptin产生神经元中依次运作，以门控，然后激活GnRH释放。我们的数据表明，青少年的约束和随后的青春期激活的时间协调介导的两个独立的神经回路在下丘脑。我们假设，kisspeptin神经元在弓状核（ARC）控制青春期的开始，而kisspeptin神经元在前腹侧室周核（AVPe）控制青春期的完成。本研究旨在验证这一假设，并分析青春期ARC和AVPe神经回路的功能作用。我们将分析ARC和AVPe kisspeptin神经元的神经回路使用遗传transneuronal追踪方法。此外，我们还将分别使用ARC和AVPe kisspeptin神经元的光遗传学激活/抑制来研究活体动物中的这些回路，同时监测动物的内分泌状态。