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

描述(申请人提供)：拟议的实验将使用一个理想的模型系统--非洲罗非鱼Astatotilapia burtoni来测量繁殖所需的高度保守的神经内分泌回路的可塑性反应。在雄性伯顿沙门氏菌中，社会地位通过大脑视前区的促性腺激素释放激素(GnRH1)神经元来调节生殖。这些神经元的大小、树突范围和活性在显性繁殖活跃的雄性中增加，在非显性雄性中减少。这些由社会地位引起的GnRH1神经元的变化是众所周知的，但在这种社会转换过程中发生的功能变化则不是很清楚。为了绘制功能变化图，我将追踪GnRH1神经元的神经元输入，比较性能力占优势的男性和性不成熟的非占优势男性的神经元。我还将对影响每种类型男性GnRH1神经元的神经递质进行高分辨率组织化学分析。我将使用一种新的新技术，阵列断层扫描，它允许在相同的大脑切片上重复进行免疫细胞化学标记。在这个唯一适合的模式生物体中，理解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可塑性的机制。性成熟是一种重要的生物学发展，它为生物体进入生殖活跃的成年生活阶段做好准备。大脑整合了复杂的社会和环境信息，以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产出和生育能力，了解控制大脑生殖结构可塑性变化的机制可能会改进生殖障碍的治疗方法，并改善公共健康。

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.