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

项目摘要/摘要 在经历有性繁殖的生物体中，生殖成功和后代的存活取决于社会 互动，当然在人类中，这些行为对我们的专业人员的心理健康和成功也是至关重要的 活着。在理解各种动物的神经系统如何变化方面取得了重大进展，从 蠕虫对哺乳动物来说，能够成功地展示社会互动。例如，在小鼠身上，神经的中枢成分 生殖行为、领土攻击性和父母照顾的基础回路在这两个地方都被清楚地识别出来 使用分子遗传学方法的雄性和雌性。最近的研究也提供了对具体程度的见解 化学感觉线索作用于这些神经回路，引导正在进行的社会互动。社交互动及其 结果是在内部感觉到的，以调节下游生物体的长期变化，但人们对此知之甚少。 哺乳动物雌性在从寻找配偶过渡到 为怀孕、分娩和随后的哺乳做准备。感觉和调节这些主要的神经回路 对过渡的描述很糟糕。我们的目标是从机械上描述这些神经回路，以便 了解他们如何感知外周和内脏生殖器官的变化，以指导随后的行为 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一组神经元，这些神经元特定地 感觉生殖行为的成功达到顶峰，而不是它之前的社会互动。在这个目标1中 项目中，我们建议成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觉到这一行为 终结点。在目标2中，我们将从功能上描述这些神经元，以了解它们对生殖后的贡献。 女性中与行为相关的转变。在目标3中，我们将描述投射目标和突触前输入， 这些神经元为了从机制上理解这个神经回路如何感知内部事件来调节这些 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交行为灵活性的神经回路机制的见解 以繁殖为中心。女性在行为和生理上也经历着重大的转变， 我们的工作有可能阐明人类生物学在健康方面的这一重要方面以及 在这一过程中，可能会影响妇女的许多疾病状况。

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 In unpublished findings, we have identified a population of neurons in the female mouse brain that specifically senses successful culmination of reproductive behavior but not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.