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: 8077251
• 负责人: Catherine Dulac
• 金额: $ 34.21万
• 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/8077251
• 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; Health; 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; 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(由申请者提供)：研究和相关的其他项目信息项目摘要/摘要研究是在这项资助下进行的，目的是表征小鼠信息素诱发行为和内分泌反应的大脑回路。最近的数据表明，嗅觉和犁鼻(VNO)系统都参与了信息素的处理，以及VNO输入在确保行为反应的性别特异性方面发挥了关键作用。这些发现提出了两个基本问题：嗅觉和VNO输入是如何整合的，以便动物获得生理上相关的反应，以及每个化学感觉系统和相关的受体在信息素处理中分别扮演什么角色。我们将研究特定的神经肽网络整合整个大脑的嗅觉和VNO信息素信号以调节繁殖和攻击性反应的假设。条件伪狂犬病病毒(PRV)和遗传操作将被用来分别追踪与参与繁殖和攻击控制的肽能神经元相关的电路，并识别特定的嗅觉和犁鼻区域以及涉及的感觉受体。嗅觉和VNO输入对未被覆盖的回路的功能贡献将通过有针对性的基因消融进一步研究。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适当行为表达的机制提供关键的见解。公共卫生相关性：研究和相关其他项目信息项目叙述识别大脑中专门负责控制生殖和攻击行为的离散神经元群体，将为开发与生育和精神疾病病理性攻击行为控制相关的新疗法提供新的和重要的见解。