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

GnRH1 神经元的输入：性行为时突触身份和连接的变化

• 批准号: 8228175
• 负责人: Russ E. Carpenter
• 金额: $ 3.17万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-28 至 2012-08-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8228175
• 关键词: Adult; African; Amino Acids; Animal Model; Antigens; Area; Behavior; Behavior Control; Behavioral; Biological; Biological Models; Brain; Brain region; Cells; Cichlids; Complex; Cues; Dendrites; Development; Disease; Event; Fertility; Fiber; Fostering; Future; Glutamates; Goals; Gonadal structure; Gonadotropin Hormone Releasing Hormone; Histological Techniques; Hormonal Change; Human; Hypothalamic structure; Image; Imagery; Individual; Label; Laboratories; Lead; Life; Mammals; Maps; Measures; Mediating; Methods; Mus; Nature; Neural Pathways; Neurobiology; Neuronal Plasticity; Neurons; Neurosecretory Systems; Neurotransmitters; Optics; Organism; Output; Peptide Receptor; Peptides; Peroxidases; Physical environment; Physiological; Pituitary Gland; Plants; Plastics; Puberty; Public Health; Reproduction; Reproductive system; Research; Resolution; Seasons; Sexual Development; Sexual Maturation; Signal Transduction; Social Behavior; Social status; Staging; Structure; Synapses; System; Techniques; Temperature; Tissues; Tracer; Transgenic Animals; Vertebrates; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; Wheat Germ Agglutinins; brain remodeling; comparative; design; flexibility; gamma-Aminobutyric Acid; human GNRH1 protein; improved; male; neural circuit; neuropeptide Y; novel; pituitary gonadal axis; receptor; relating to nervous system; reproductive; reproductive function; research study; response; social; social integration; social stress; teleost fish; tomography

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.

描述（由申请人提供）：拟议的实验将使用非常适合的模型系统（非洲丽鱼科鱼，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A. burtoni中，社会地位通过大脑视前区的促性腺激素释放激素（GnRH1）神经元调节繁殖。这些神经元的大小、树突范围和活性在占优势、生殖活跃的雄性中增加，而在非占优势的雄性中减少。这些社会地位引起的 GnRH1 神经元变化是众所周知的，但在这种社会转变过程中发生的功能变化却鲜为人知。为了绘制功能变化图，我将追踪 GnRH1 神经元的神经元输入，将具有性能力的优势雄性的输入与性不成熟的非优势雄性的输入进行比较。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。我将使用一种新颖的技术，即阵列断层扫描，它允许在同一脑切片上重复进行免疫细胞化学标记。了解这种独特的模型生物体中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。性成熟是一种重要的生物发育，它为生物体进入生殖活跃的成年生命阶段做好准备。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能力，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。