Genomic and neural circuit characterization of interoceptive experience-modulated female behavior in mice

小鼠内感受体验调节雌性行为的基因组和神经回路特征

• 批准号: 10586990
• 负责人: Nirao Mahesh Shah
• 金额: $ 49.26万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10586990
• 关键词: 4-Hydroxy-Tamoxifen; Aggressive behavior; Animals; Architecture; Behavior; Behavioral; Brain; Candidate Disease Gene; Caring; Cell Nucleus; Cells; Childbirth; Conceptions; Cues; Data; Discipline of Nursing; Disease; Ejaculation; Embryo; Event; Exhibits; Female; Fiber; Fluorescent in Situ Hybridization; Genomics; Goals; Halorhodopsins; Health; Heterogeneity; Human; Human Biology; Image; Kinetics; Label; Light; Mammals; Maps; Mediating; Molecular; Molecular Genetics; Mothers; Mus; Nervous System; Neural Pathways; Neurons; Neurosciences; Newborn Infant; Organism; Outcome; Partner in relationship; Peripheral; Personal Satisfaction; Photometry; Physiological; Physiology; Population; Pregnancy; Process; Rabies; Reproduction; Reproductive Behavior; Resolution; Sensory; Series; Sexual Abstinence; Sexual Reproduction; Social Behavior; Social Interaction; Specificity; Structure of terminal stria nuclei of preoptic region; Territoriality; Testing; Transgenes; Uterus; Viral; Viscera; Visceral; Well in self; Woman; Work; cost; experience; experimental study; flexibility; genetic approach; implantation; in vivo; insight; male; neural circuit; optogenetics; postsynaptic; presynaptic; reproductive; reproductive organ; reproductive success; response; sensor; single nucleus RNA-sequencing; success

PROJECT SUMMARY/ABSTRACT Reproductive success and survival of progeny in organisms that undergo sexual reproduction are contingent on social interactions, and in humans of course these behaviors are also critical for mental well-being and success in our professional lives. There have been significant advances in understanding how the nervous system of diverse animals, ranging from worms to mammals, enables successful display of social interactions. In mice for example, central components of neural circuits underlying reproductive behavior, territorial aggression, and parental care have been clearly identified in both males and females using molecular genetic approaches. Recent studies have also provided insights into how specific chemosensory cues act on these neural circuits to guide ongoing social interactions. How social interactions and their outcomes are internally sensed to modulate downstream long term changes in the organism is less well understood. Mammalian females show dramatic changes following reproductive behavior as they transition from seeking mates to preparing for pregnancy, childbirth, and subsequent nursing. The neural circuits that sense and mediate these major transitions are poorly characterized. Our goal is to characterize these neural circuits mechanistically in order to understand how they sense changes in peripheral, visceral reproductive organs to guide subsequent behavioral transitions. In unpublished findings, we have identified a population of neurons in the female mouse brain that specifically senses successful culmination of reproductive behavior but not the social interactions that precede it. In Aim 1 of this project, we propose to image ongoing activity of these neurons to define how and when they sense this behavioral endpoint. In Aim 2, we will functionally characterize these neurons to understand their contribution to post-reproductive behavior related transitions in females. In Aim 3, we will characterize projection targets of, and presynaptic inputs to, these neurons in order to understand mechanistically how this neural circuit senses an internal event to mediate these transitions; in addition, we will use molecular genetic approaches to determine the identity of these neurons. If successful, our project will provide insights into neural circuit mechanisms that regulate flexibility in female mouse social behaviors centered around reproduction. Women also experience major transitions in behavior and physiology centered around reproduction, and our work has the potential to shed light on this important aspect of human biology in health as well as potentially the many disease conditions that can impact women during this process.

项目总结/摘要 在有性繁殖的生物体中，繁殖成功和后代的存活取决于社会因素。 当然，在人类中，这些行为对我们的心理健康和职业成功也至关重要。 生活在理解不同动物的神经系统如何变化方面已经取得了重大进展， 从蠕虫到哺乳动物，都能成功地展示社会互动。例如，在小鼠中， 生殖行为、领土侵略和父母照顾的潜在回路在两种情况下都被清楚地确定下来。 男性和女性使用分子遗传学方法。最近的研究也提供了关于如何具体 化学感觉线索作用于这些神经回路，以指导正在进行的社会互动。社会互动和他们的 结果被内部感知以调节下游生物体中的长期变化还不太清楚。 哺乳动物雌性在从寻找配偶过渡到寻找配偶的过程中， 为怀孕、分娩和随后的哺乳做准备。感知和调节这些主要的神经回路 过渡的特征很差。我们的目标是从机制上描述这些神经回路， 了解他们如何感知外周、内脏生殖器官的变化，以指导随后的行为 过渡。在未发表的研究结果中，我们已经确定了雌性小鼠大脑中的一群神经元， 感觉到生殖行为的成功高潮，但不是在此之前的社会互动。 项目，我们建议对这些神经元的持续活动进行成像，以确定它们如何以及何时感知到这种行为 终点。在目标2中，我们将在功能上表征这些神经元，以了解它们对生殖后的贡献。 与女性行为有关的转变。在目标3中，我们将描述投射目标和突触前输入， 这些神经元，以了解机械神经回路如何感觉到内部事件，以调解这些 此外，我们将使用分子遗传学方法来确定这些神经元的身份。如果成功， 我们的项目将提供对调节雌性小鼠社会行为灵活性的神经回路机制的深入了解。 围绕着繁殖。女性在行为和生理上也经历了主要的转变， 生殖，我们的工作有可能揭示人类生物学在健康以及 在这一过程中可能影响妇女的许多疾病。