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：
10762996
负责人：
Nirao Mahesh Shah
金额：
$ 49.27万
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/10762996
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.

项目概要/摘要进行有性繁殖的生物体的繁殖成功和后代的存活取决于社会当然，对于人类来说，这些行为对于心理健康和职业成功也至关重要。生活。在了解不同动物的神经系统如何运作方面已经取得了重大进展，从从蠕虫到哺乳动物，能够成功展示社交互动。例如，在小鼠中，神经元的中心成分生殖行为、领地攻击和亲代抚育背后的回路在这两种动物中都已被清楚地识别出来。使用分子遗传学方法的男性和女性。最近的研究还提供了关于具体如何化学感应信号作用于这些神经回路，以指导正在进行的社交互动。社交互动如何及其结果是内部感知的，以调节生物体下游的长期变化，但目前尚不清楚。哺乳动物雌性在生殖行为之后表现出巨大的变化，因为它们从寻找配偶过渡到为怀孕、分娩和随后的哺乳做准备。感知和介导这些主要的神经回路过渡的特征很差。我们的目标是机械地表征这些神经回路，以便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，这些神经元专门负责感觉到生殖行为的成功顶峰，而不是之前的社会互动。在这个目标1中项目中，我们建议对这些神经元的持续活动进行成像，以定义它们如何以及何时感知这种行为端点。在目标 2 中，我们将从功能上表征这些神经元，以了解它们对生殖后的贡献女性行为相关的转变。在目标 3 中，我们将描述投射目标和突触前输入的特征，这些神经元，以便从机制上理解该神经回路如何感知内部事件来调节这些过渡；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。如果成功的话，我们的项目将深入了解调节雌性小鼠社交行为灵活性的神经回路机制以繁殖为中心。女性还经历着行为和生理方面的重大转变生殖，我们的工作有可能揭示人类生物学在健康和健康方面的这一重要方面在此过程中可能会影响女性的许多疾病。