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

点击翻译按钮获取中文摘要

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.