Neural processing of status signals in social hierarchies

社会等级中状态信号的神经处理

• 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
• 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

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 社会知觉是社会交往的一个基本特征。识别社交线索的能力 其他人对形成有意义的社会关系至关重要。社会知觉缺陷可能会导致 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很明显。在社会等级制度中，个人 需要识别与状态(状态信号)相关的社交提示，并使用此信息来确定它们如何 社交互动。然而，我们对大脑如何接收和转换状态信号的知识 有社交能力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，每个人都有唯一的等级，并表现出适当的社会地位 对排名较高和较低的个体的行为。我们还发现杏仁内侧核(MEA)和 腹侧乳头体前核(PMV)在个体暴露时表现出不同的神经活动模式 主导与从属嗅觉状态信号之间的关系。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，负责处理以前的社会状态信息 将输出信号发送到引导行为表达的下丘脑下游核团。 我们将结合我们创新的社会等级模式和尖端的分子工具来测试这一点 男性和女性的假说。在特定的目标1中，我们将测试mea和pmv是否含有神经元。 对状态信号敏感的亚群。使用单核RNA-Seq(SnRNA-Seq)，我们将 检测MEA和PMV细胞的转录活性。应用细胞房室分析的时间序列 荧光原位杂交结合RNAScope的活性我们将表征空间 以及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 将能够确定不同的或重叠的神经元亚群是否处理主导和从属 社交信号。在特定的目标2，我们将使用活体吗啉直接测试催产素和 MEA和PMV中的加压素受体在协调社会地位知觉中的作用。这些受体有一种 在社会行为中的既定角色，并在mea和pmv中表现出来。我们将有选择地降低 翻译每种受体类型，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支配关系方面。如果成功，这些研究的结果 将建立一种新的范式来理解社会知觉的神经加工，建立方法 和PMV作为辨别社会信号的关键大脑区域，识别出 对状态提示作出反应，并确定催产素和加压素1a受体在这些区域的作用 将社交信号转化为与背景相适应的社交行为。这项工作将为我们提供强大的 为研究社会知觉的神经生物学的富有成效的研究计划奠定基础。