Input to GnRH1 neurons: Changes in synaptic identity and connectivity at sexual m

描述（由申请人提供）：拟议的实验将测量高度保守的神经内分泌回路的塑性反应，这是繁殖所必需的，使用理想的合适的模型系统，非洲丽鱼，波托尼Astatotilapia。在雄性波氏盲蝽中，社会地位通过大脑视前区促性腺激素释放激素（GnRH1）神经元调节生殖。这些神经元的大小、树突范围和活性在繁殖活跃的优势雄性中增加，而在非优势雄性中减少。这些社会地位引起的GnRH1神经元的变化是众所周知的，但是在这种社会转换过程中发生的功能变化却不为人所知。为了绘制功能变化图，我将追踪神经元输入到GnRH1神经元，比较有性能力的优势雄性和性不成熟的非优势雄性的神经元。我还将对影响每种男性GnRH1神经元的神经递质进行高分辨率组织化学分析。我将使用一种新的技术，阵列断层扫描，它允许在相同的大脑切片上重复免疫细胞化学标记。了解这种独特的适合模式生物的社会地位变化引起的神经可塑性，将确定社会行为控制生殖系统神经元可塑性的机制。性成熟是一项重要的生物学发育，为生物体进入繁殖活跃的成年阶段做准备。大脑整合复杂的社会和环境信息来启动和管理支持这一事件的神经和激素变化。由于GnRH1系统控制着包括人类在内的所有脊椎动物的生殖输出和生育力，了解控制大脑生殖结构可塑性变化的机制可能会改善生殖疾病的治疗方法，并改善公众健康。

DESCRIPTION (provided by applicant): The proposed experiments will measure the plastic responses of a highly conserved neuroendocrine circuit necessary for reproduction using an ideally suited model system, the African cichlid fish, Astatotilapia burtoni. In male A. burtoni, social status regulates reproduction via gonadotropin releasing hormone (GnRH1) neurons in the pre-optic area of the brain. The size, dendritic extent and activity of these neurons increase in dominant, reproductively active males and decrease in non dominant males. These social status-induced changes in GnRH1 neurons are well known, however the functional changes that occur during this social conversion are not. To map the functional changes, I will trace neuronal inputs to GnRH1 neurons, comparing those of sexually competent dominant males with those of sexually immature non dominant males. I will also perform a high resolution histochemical analysis of neurotransmitters that influence GnRH1 neurons in each type of male. I will use a novel new technique, array tomography, that allows repeated immunocytochemical labeling on the same brain sections. Understanding the neural plasticity induced by social status change in this uniquely suited model organism will identify the mechanism through which social behavior controls neuronal plasticity of the reproductive system. Sexual maturation is an important biological development that prepares an organism for reproductively active adult life stages. The brain integrates complex social and environmental information to initiate and manage the neural and hormonal changes that support this event. As the GnRH1 system controls reproductive output and fertility in all vertebrates, including humans, understanding the mechanisms that control plastic changes in the reproductive structures of the brain may lead to improved therapies for reproductive disorders, and improve public health.