Neural processing of status signals in social hierarchies

社会等级中状态信号的神经处理

基本信息

批准号：
10646570
负责人：
James Patrick Curley
金额：
$ 25.26万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10646570
关键词：
Address Affect Amygdaloid structure Animals Behavior Behavioral Brain Brain region Cell Nucleus Cellular Compartment Analysis Characteristics Complex Cues Data Set Emotional Environment Exposure to Female Fluorescent in Situ Hybridization Foundations Gene Expression Gene Expression Profile Genes Genetic Transcription Genomics Housing Human Hypothalamic structure Impairment In Situ Hybridization Individual Knowledge Loneliness Measures Medial Molecular Mus Neurobiology Neurodevelopmental Disorder Neurons Neuropeptide Receptor Neurosciences Odors Output Oxytocin Oxytocin Receptor Pathway interactions Pattern Perception Personal Satisfaction Population Primates Process Productivity Regulation Research Rodent Role Sensory Signal Transduction Social Behavior Social Change Social Discrimination Social Dominance Social Environment Social Hierarchy Social Interaction Social Perception Social status Stimulus System Techniques Testing Time Transcriptional Activation Translational Repression Translations Vasopressin Receptor Vasopressins Well in self Work autism spectrum disorder behavior test brain cell differential expression innovation male multidisciplinary neural neural patterning novel programs receptor response sex single nucleus RNA-sequencing social social communication social relationships tool transcriptomic profiling

项目摘要

PROJECT SUMMARY/ABSTRACT Social perception is a fundamental feature of social communication. The ability to recognize social cues of others is critical to forming meaningful social relationships. Deficits in social perception can lead to impaired social coordination, resulting in loneliness and isolation that severely impacts well-being. This coordination is evident within the dynamic social interactions that occur in social hierarchies. In social hierarchies, individuals need to recognize social cues related to status (status signals) and use this information to determine how they socially interact. However, our knowledge of how the brain receives and transforms status signals into socially competent behavioral output remains limited. We have demonstrated that male and female mice form highly linear social hierarchies where each individual has a unique rank and shows appropriate social behavior to higher and lower ranked individuals. We have also found that the medial amygdala (MeA) and the ventral premammillary nucleus (PmV) show differential patterns of neural activity when individuals are exposed to dominant versus subordinate olfactory status signals. Based on these findings we hypothesize that social signal responsive neurons exist in the MeA and PmV that processes social status information before sending outputs to downstream hypothalamic nuclei which guide the expression of behavior. We will combine our innovative social hierarchy paradigm with cutting-edge molecular tools to test this hypothesis in males and females. In Specific Aim 1, we will test if the MeA and PmV contain neuronal subpopulations that are sensitive to status signals. Using single nucleus RNA-Seq (snRNA-Seq) we will measure the transcriptional activation of MeA and PmV cells. Using cellular compartment analysis of temporal activity by fluorescent in situ hybridization (catFISH) in conjunction with RNAScope we will characterize spatial and temporal transcription patterns in the MeA and PmV in response to status signals. Using this approach, we will be able to determine if distinct or overlapping neuronal subpopulations process dominant and subordinate social signals. In Specific Aim 2, we will use vivo morpholinos to directly test the role of oxytocin and vasopressin receptors in the MeA and PmV in coordinating social status perception. These receptors have a well-established role in social behavior and are expressed in the MeA and PmV. We will selectively reduce the translation of each receptor type, and then test how this manipulation impacts the ability of animals to engage in social discrimination and maintain social dominance relationships. If successful, results from these studies will establish a novel paradigm for understanding the neural processing of social perception, establish the MeA and PmV as key brain regions in the discrimination of social signals, identify subpopulations of neurons that respond to status cues, and determine the roles of oxytocin and vasopressin 1a receptors in these regions in transforming social signals into contextually appropriate social behavior. This work will provide a strong foundation for a productive research program investigating the neurobiology of social perception.

项目摘要/摘要社会感知是社会交流的基本特征。认识社会提示的能力其他人对于建立有意义的社会关系至关重要。社会感知的缺陷会导致受损社会协调，导致孤独和孤立，严重影响幸福感。这种协调是在社会等级制度中发生的动态社会互动中可以明显看出。在社会等级中，个人需要识别与状态有关（状态信号）有关的社交提示，并使用此信息来确定他们如何社交互动。但是，我们对大脑如何接收和将状态信号转化为社会上胜任的行为产出仍然有限。我们已经证明了雄性和雌性小鼠形成高度线性的社会等级制度，每个人都有独特的等级并显示适当的社会对更高和较低的个人的行为。我们还发现内侧杏仁核（MEA）和当个体暴露时，腹腹前核（PMV）显示出神经活动的差异模式主导与下属嗅觉状态信号。根据这些发现，我们假设社会在MEA和PMV中存在信号反应性神经元，该神经元之前处理社交状况信息之前将输出发送到下游下丘脑核，以指导行为的表达。我们将将创新的社会等级制度范式与尖端的分子工具结合起来，以测试这一点男性和女性的假设。在特定目标1中，我们将测试MEA和PMV是否包含神经元对状态信号敏感的亚群。使用单核RNA-seq（SnRNA-Seq），我们将测量MEA和PMV细胞的转录激活。使用时间的细胞室分析通过荧光原位杂交（cat鱼）与rnascope结合的活性，我们将表征空间 MEA和PMV中的时间转录模式响应状态信号。使用这种方法，我们将能够确定不同或重叠的神经元亚群是主要和下属的社会信号。在特定的目标2中，我们将使用体内形态学直接测试催产素和 MEA中的加压素受体和PMV协调社会地位感知。这些受体有一个在社会行为中成熟的角色，并在MEA和PMV中表达。我们将有选择地减少每种受体类型的翻译，然后测试这种操作如何影响动物参与的能力在社会歧视和维持社会主导关系中。如果成功，这些研究的结果将建立一个新颖的范式来理解社会感知的神经处理，建立MEA 在歧视社会信号中，PMV作为关键大脑区域，确定神经元的亚群响应状态提示，并确定催产素和加压素1a受体在这些区域中的作用将社会信号转变为上下文适当的社会行为。这项工作将提供强大的研究社会感知神经生物学的生产研究基金会。