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: 8481529
• 负责人: Catherine Dulac
• 金额: $ 32.5万
• 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/8481529
• 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; genetic analysis; genetic manipulation; improved; insight; kisspeptin; male; neural circuit; novel; olfactory receptor; paraventricular nucleus; prospective; receptor; recombinase; response; sex; tool; virus genetics

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.

在此资助下进行的研究旨在描述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，参与嗅觉和犁鼻（VNO）系统在信息素处理和VNO输入的关键作用，以确保性别特异性的行为反应。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的反应，以及每个化学感受系统和相关受体在信息素处理中的各自作用是什么。我们将调查的假设，即特定的神经肽网络整合整个大脑的嗅觉和VNO信息素信号，以介导生殖和侵略性的反应。条件性伪狂犬病病毒（PRV）和遗传操作将被用来跟踪电路与肽能神经元参与控制的繁殖和侵略，分别，并确定具体的嗅觉和犁鼻区域和感觉受体参与。嗅觉和VNO输入的功能性贡献的未覆盖的电路将进一步调查有针对性的基因消融。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。

项目成果

Superresolution imaging of chemical synapses in the brain.

• DOI: 10.1016/j.neuron.2010.11.021
• 发表时间: 2010-12-09
• 期刊: NEURON
• 影响因子: 16.2
• 作者: Dani, Adish;Huang, Bo;Bergan, Joseph;Dulac, Catherine;Zhuang, Xiaowei
• 通讯作者: Zhuang, Xiaowei

Sex-specific processing of social cues in the medial amygdala.

• DOI: 10.7554/elife.02743
• 发表时间: 2014-06-03
• 期刊: eLife
• 影响因子: 7.7
• 作者: Bergan JF;Ben-Shaul Y;Dulac C
• 通讯作者: Dulac C

The activity-dependent histone variant H2BE modulates the life span of olfactory neurons.

• DOI: 10.7554/elife.00070
• 发表时间: 2012-12-13
• 期刊: eLife
• 影响因子: 7.7
• 作者: Santoro SW;Dulac C
• 通讯作者: Dulac C

Neural control of maternal and paternal behaviors.

• DOI: 10.1126/science.1253291
• 发表时间: 2014-08-15
• 期刊: Science (New York, N.Y.)
• 作者: Dulac C;O'Connell LA;Wu Z
• 通讯作者: Wu Z