Microbiota and Neural Circuits controlling Social Behavior

 描述(由申请人提供)：最近突破性的研究表明，生活在消化道(肠道微生物区系)的微生物群落在以情绪和社会反应紊乱为特征的精神疾病中发挥着关键作用。在了解神经控制焦虑和社会行为方面也取得了加速进展，特别是在“社会神经肽”、加压素和催产素的作用方面。到目前为止，还没有人将这两个令人兴奋的领域联系起来。两个专业领域互补的老牌实验室已经联手承担这项任务：一个专注于大脑中的性别差异和社会行为的神经基础，另一个专注于微生物群和肠道健康之间关系的分子途径。这些实验室将共同开发小鼠模型，以检验肠道微生物群在生命早期起作用的总体假设 对加压素和催产素系统以及由这些系统控制的焦虑相关和社交行为进行永久性编程。在第一个实验中，在无菌小鼠出生时被两个品系的小鼠中的任何一个在社交和焦虑相关行为以及微生物群组成方面存在显著差异的肠道微生物群定植后，将比较它们在发育期间和成年时的大脑和行为。第二个实验利用了两个参与实验室中的一个实验室最近的一项发现，即常用的食品添加剂，即乳化剂，具有令人惊讶的强大效果 通过作用于微生物区系组成及其与寄主的相互作用来研究生理学。初步数据表明，这些影响将延伸到大脑和行为，这将在当前的项目中进行测试。总之，这个项目将利用生理学上的相关方法，解决我们对肠道-脑轴及其在焦虑相关和社交行为发展中的作用的理解方面的一个关键差距。这些发现将使后续识别影响焦虑相关行为和社交行为的特定微生物区系，以及涉及的信号通路成为可能。此外，研究微生物区系对加压素和催产素表达的影响将不仅仅是了解微生物区系对行为的影响，还包括微生物区系对自主神经功能、代谢综合征和疼痛的影响，所有这些都受到微生物区系的影响并受这些肽的调节。

 DESCRIPTION (provided by applicant): Groundbreaking recent studies indicate that the community of microorganisms living in the digestive tract (the gut microbiota) plays a key role in psychiatric illnesses characterized by disordered emotional and social responses. Accelerated progress has also been made in understanding neural control of anxiety and social behavior, especially with regard to the roles of the `social neuropeptides,' vasopressin and oxytocin. To date nobody has linked these two exciting fields. Two established laboratories with complementary areas of expertise have joined forces to take on this task: one focused on sex differences in the brain and the neural basis of social behavior, the other on molecular pathways underlying the relationship between the microbiome and gut health. Together, these laboratories will develop mouse models to test the overall hypothesis that the gut microbiota acts early in life to permanently program vasopressin and oxytocin systems as well as anxiety- related and social behaviors controlled by these systems. In the first experiment, brain and behavior will be compared during development and in adulthood of germ-free mice after they have been colonized at birth by gut microbiota derived from either of two strains of mice that differ significantly in social and anxiety-related behaviors as well as composition of the microbiome. The second experiment takes advantage of a recent discovery in one of the two participating laboratories that commonly used food additives, i.e., emulsifiers, have surprisingly strong effects on physiology by acting on microbiota composition and its interaction with the host. Preliminary data suggest that these effects extend to the brain and behavior, which will be tested in the current project. Together, this project will address a crucial gap in our understanding of the gut-brain axis and its role in the development of anxiety-related and social behaviors, using physiologically relevant approaches. The findings will make possible subsequent identification of the specific microbiota affecting anxiety-related and social behaviors, and the signaling pathways involved. In addition, the payoff for studying effects of the microbiota on vasopressin and oxytocin expression will go beyond understanding microbiota effects on behavior, to include effects of the microbiota on autonomic functions, metabolic syndrome, and pain, all of which are affected by microbiota and modulated by these peptides.