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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要/摘要在经历有性繁殖的有机体中后代的生殖成功和生存，取决于社会互动，在人类中，这些行为对于我们的专业人士的心理健康和成功也至关重要生命。在理解各种动物的神经系统从范围从对哺乳动物的蠕虫，可以成功展示社交互动。例如，在小鼠中，神经的中央组成部分在两者中都清楚地确定了生殖行为，领土侵略和父母护理的基础电路雄性和女性使用分子遗传学方法。最近的研究还提供了有关如何具体的见解化学意识对这些神经回路作用，以指导正在进行的社交互动。社交互动及其如何在内部感觉到结果可以调节生物体的下游长期变化的理解率不高。哺乳动物雌性从寻求伴侣过渡到生殖行为后显示出巨大的变化准备怀孕，分娩和随后的护理。感知并调解这些主要的神经回路过渡的特征很差。我们的目标是以机械的方式来表征这些神经回路了解他们如何感觉到外围，内脏生殖器官的变化以指导后续行为过渡。在未发表的发现中，我们已经确定了雌性小鼠大脑中的神经元群感觉到成功的生殖行为的最高点，而不是在其之前的社会互动。在目标1中项目，我们建议图像这些神经元正在进行的活动，以定义它们如何以及何时感知这种行为端点。在AIM 2中，我们将在功能上表征这些神经元，以了解它们对后生化的贡献女性中与行为相关的过渡。在AIM 3中，我们将以突触的投影目标和突触前的投影目标为特征这些神经元为了机械理论地了解该神经回路如何感知内部事件以调节这些事件过渡；此外，我们将使用分子遗传方法来确定这些神经元的身份。如果成功，我们的项目将提供有关调节女性鼠标社交行为灵活性的神经回路机制的见解以繁殖为中心。妇女还经历了以行为和生理学的重大转变繁殖，我们的工作有可能阐明人类生物学在健康中的这一重要方面可能在此过程中可能影响女性的许多疾病。