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.

项目概要/摘要社会感知是社会沟通的基本特征。识别社交线索的能力其他人对于形成有意义的社会关系至关重要。社会认知的缺陷可能会导致社会协调，导致孤独和孤立，严重影响福祉。这种协调是在社会等级制度中发生的动态社会互动中显而易见。在社会等级制度中，个人需要识别与状态（状态信号）相关的社交线索，并使用此信息来确定他们如何进行社交互动。然而，我们对大脑如何接收状态信号并将其转化为信号的了解具有社会能力的行为输出仍然有限。我们已经证明雄性和雌性小鼠形成高度线性的社会等级制度，其中每个人都有独特的等级并表现出适当的社会地位对级别较高和级别较低的个人的行为。我们还发现内侧杏仁核 (MeA) 和当个体暴露时，腹侧前乳头核（PmV）表现出不同的神经活动模式主导与从属嗅觉状态信号。基于这些发现，我们假设社会信号反应神经元存在于 MeA 和 PmV 中，它们在处理社会状态信息之前将输出发送到指导行为表达的下游下丘脑核团。我们将把我们创新的社会等级范式与尖端的分子工具结合起来来测试这一点男性和女性的假设。在具体目标 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。使用时间细胞区室分析通过荧光原位杂交 (catFISH) 结合 RNAScope 来表征空间活性 MeA 和 PmV 中响应状态信号的时间转录模式。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否处理主导和从属社会信号。在Specific Aim 2中，我们将使用vivo morpholinos直接测试催产素和 MeA 和 PmV 中的加压素受体协调社会地位感知。这些受体具有在社会行为中的明确作用并在 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社会歧视并维持社会支配关系。如果成功，这些研究的结果将建立一个新的范式来理解社会感知的神经处理，建立 MeA 和 PmV 作为区分社交信号的关键大脑区域，识别神经元亚群对状态提示做出反应，并确定这些区域中催产素和加压素 1a 受体的作用将社交信号转化为适合情境的社交行为。这项工作将提供强有力的为调查社会感知的神经生物学的富有成效的研究计划奠定了基础。