Functional characterization of GnRH receptor neurons and their neural circuitry in the mouse brain

由哺乳动物释放的信息素触发先天行为，从雄性间的攻击到雌性对雄性坐骑的反应。这些行为的刻板性意味着它们是由中枢神经系统（CMS）中的硬连线神经回路介导的。阐明这些行为回路的设计和神经元组成可能有助于详细了解行为背后的机制。信息素对生殖行为和生理的影响与促性腺激素释放激素（GnRH）有关，这是一种由下丘脑神经元产生的肽。除了诱导垂体释放促性腺激素外，GnRH还通过下丘脑中的神经回路刺激雄性和雌性哺乳动物的生殖行为。我们最近使用遗传transneuronal示踪可视化小鼠GnRH神经元的神经回路。我们确定了上游神经元传递信息素的GnRH神经元。我们还可视化了下游神经元在大量区域中接收来自GnRH神经元的信息。这些神经元的一个子集表达GnRH受体，这增加了GnRH肽在CMS内局部释放的可能性，并且肽的释放可能导致下游神经元的神经元激活。本实验旨在研究小鼠CMS中GnRH受体表达神经元（GnRH-R）的功能特征。我们想研究GnRH-R在神经元和神经元隔室中的定位。我们还想知道GnRH受体神经元是如何被激活的，并描述它们的神经回路。为了能够解决这些问题，我们将在转基因小鼠中用三种不同的标记蛋白标记GnRH-R神经元。我们期望GnRH-R神经元及其神经回路的功能表征将有助于详细了解GnRH肽在大脑中的作用，并揭示小鼠生殖行为的潜在机制。

Pheromones released by mammals trigger innate behaviors ranging from intermale aggression to female Lordosis in response to male mounting. The stereotypy of these behaviors implies that they are mediated by hard-wired neural circuits in the central nervous system (CMS). Elucidating the design and neuronal composition of these behavioral circuits may significantly contribute to a detailed understanding of the mechanisms underlying behavior. Effects of pheromones on reproductive behavior and physiology have been linked to gonadotropin releasing hormone (GnRH), a peptide produced by a subset of neurons in the hypothalamus. In addition to inducing gonadotropin release from the pituitary, GnRH stimulates reproductive behaviors in both male and female mammals via neural circuits in the hypothalamus. We have recently used genetic transneuronal tracing to visualize the neural circuitry of GnRH neurons in mice. We identified upstream neurons relaying pheromonal information to GnRH neurons. We also visualized downstream neurons receiving information from GnRH neurons in a surprisingly large number of areas. A subset of these neurons expresses the GnRH receptor raising the possibility that the GnRH peptide is released locally within the CMS and that release of the peptide may lead to neuronal activation of downstream neurons. The experiments proposed here are aimed to functionally characterize GnRH receptor expressing neurons (GnRH-R) in the CMS of the mouse. We would like to investigate the localization of GnRH-R to neurons and neuronal compartments. We would also like to know how GnRH receptor neurons are activated and characterize their neural circuitry. To be able to adress these questions, we will tag GnRH-R neurons with three different marker proteins in transgenic mice. We expect that functional characterization of GnRH-R neurons and their neural circuitry will contribute to a detailed understanding of the role of GnRH peptide in the brain and unravel mechanisms underlying reproductive behavior in mice.