Genetic analysis of brain circuits underlying pheromone signaling

信息素信号传导脑回路的遗传分析

• 批准号: 7730700
• 负责人: Catherine Dulac
• 金额: $ 35.7万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7730700
• 关键词: Ablation; Afferent Pathways; Aggressive behavior; Animals; Area; Argipressin; Behavior; Behavioral; Brain; Cell Nucleus; Contraceptive methods; Data; Development; Disease; Endocrine; Ensure; Female; Fertility; Genetic; Grant; Individual; Injection of therapeutic agent; Label; Mediating; Mus; Neurons; Neuropeptides; Neurosecretory Systems; Oxytocin; Pathway interactions; Pheromone; Play; Population; Process; Psyche structure; Publishing; Regulation; Reporter; Reproduction; Research; Role; Sensory; Sensory Receptors; Sex Behavior; Signal Transduction; Social Behavior; Specificity; Suid Herpesvirus 1; Synapses; System; Transcript; Transgenic Mice; Viral; abstracting; genetic analysis; genetic manipulation; improved; insight; kisspeptin; male; neural circuit; novel; olfactory receptor; paraventricular nucleus; prospective; public health relevance; receptor; recombinase; response; sex; tool; virus genetics

Description (provided by applicant): Research and Related Other Project Information Project Summary/Abstract Studies conducted under this grant are aimed at characterizing brain circuits underlying pheromone- evoked behaviors and endocrine responses in the mouse. Recent data has demonstrated the involvement of both olfactory and vomeronasal (VNO) systems in pheromone processing and the key role of VNO inputs in ensuring the sex specificity of behavioral responses. These findings raise two fundamental questions: how are olfactory and VNO inputs integrated in order for the animal to achieve physiologically relevant responses, and what is the respective role of each chemosensory system and associated receptors in pheromone processing. We will investigate the hypothesis that specific neuropeptide networks integrate both olfactory and VNO pheromone signals throughout the brain in order to mediate reproduction and aggressive responses. Conditional pseudorabies virus (PRV) and genetic manipulations will be used to trace circuits associated with peptidergic neurons involved in the control of reproduction and aggression, respectively, and to identify specific olfactory and vomeronasal areas and sensory receptors involved. The functional contribution of olfactory and VNO inputs to the uncovered circuits will be further investigated by targeted genetic ablations. These studies will provide critical insights into the mechanisms by which the brain integrates distinct sensory information to regulate the neuroendocrine axis and the expression of appropriate behaviors. PUBLIC HEALTH RELEVANCE: Research and Related Other Project Information Project Narrative The identification of discrete populations of neurons across the brain that are specifically engaged in the control of reproduction and aggression should provide new and significant insights for the development of novel therapies related to fertility and the control of pathological aggressive behavior in mental diseases.

描述（由申请人提供）：研究及相关的其他项目信息项目摘要/摘要研究旨在表征鼠标中诱发的信息素行为和内分泌反应的脑电路。最近的数据表明，嗅觉和呕吐物（VNO）系统参与了信息素处理，以及VNO输入在确保行为反应的性别特异性中的关键作用。这些发现提出了两个基本问题：为了使动物获得生理相关的反应，嗅觉和VNO输入是如何整合的，以及每个化学体系系统和相关受体在信息素处理中的各自作用是什么。我们将研究以下假设：特定的神经肽网络在整个大脑中都整合嗅觉和VNO信息素信号，以介导繁殖和攻击性反应。有条件的伪标记病毒（PRV）和遗传操纵将用于跟踪与涉及繁殖和攻击性控制的肽基神经元相关的电路，并确定涉及的特定嗅觉和呕吐区和呕吐区和感觉受体。靶向遗传消融将进一步研究嗅觉和VNO输入对未发现电路的功能贡献。这些研究将为大脑整合不同的感觉信息以调节神经内分泌轴和表达适当行为的机制提供关键的见解。公共卫生相关性：研究及相关的其他项目信息项目叙述，识别专门参与繁殖和侵略控制的整个大脑神经元的离散种群，应为发展与生育能力和病理侵略行为相关的新疗法的发展提供新的和重要的见解。