Genetic analysis of brain circuits underlying pheromone signaling

项目摘要/摘要本项目资助的研究旨在描述信息素诱发行为和内分泌反应背后的大脑回路。最近的数据表明，嗅觉和犁鼻（VNO）系统都参与信息素的加工，并且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输入如何整合以使动物实现生理相关反应，以及每种化学感觉系统和相关受体在信息素加工中的各自作用。我们将研究特定神经肽网络在整个大脑中整合嗅觉和VNO信息素信号以介导繁殖和攻击反应的假设。条件性伪狂犬病毒（PRV）和基因操作将分别用于追踪与控制繁殖和攻击有关的肽能神经元相关的回路，并确定特定的嗅觉和犁鼻区以及相关的感觉受体。嗅觉和VNO输入对未发现回路的功能贡献将通过靶向遗传消融进一步研究。这些研究将为大脑整合不同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重要见解。公共卫生相关性：研究和相关其他项目信息项目描述识别大脑中专门参与生殖和攻击控制的离散神经元群，应该为开发与生育和精神疾病病理攻击行为控制相关的新疗法提供新的和重要的见解。

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.