Establishing Neural Control Systems for Social Homeostasis

建立社会稳态的神经控制系统

• 批准号: 10615841
• 负责人: Jenna Ann McHenry
• 金额: $ 52.9万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615841
• 关键词: Address; Adult; Aggressive behavior; Animals; Autonomic nervous system disorders; Behavior; Behavior Control; Behavioral; Biological; Body Temperature; Brain; Brain Diseases; Brain Mapping; Calcium; Caring; Cells; Cognitive; Communities; Complex; Confusion; Data; Disease; Eating; Elements; Emotional; Equilibrium; Event; Experimental Models; Female; Food; Genetic; Genetic Recombination; Head; Health; Heart Diseases; Homeostasis; Human; Hunger; Hypothalamic structure; Image; Imaging technology; Immune; Immune System Diseases; Impairment; Individual; Individual Differences; Insecta; Link; Literature; Location; Loneliness; Maps; Medial; Mediating; Medical; Mental Depression; Mental Health; Metabolic; Metabolic Diseases; Methodology; Microscope; Modeling; Mood Disorders; Mus; Nature; Neurons; Neurosciences; Organ; Partner in relationship; Pathologic; Phenotype; Physiological; Play; Population; Population Dynamics; Positioning Attribute; Positive Valence; Predisposition; Premature Mortality; Preoptic Areas; Process; Psychoses; Resources; Role; Sensory; Series; Sleep; Sleep Disorders; Social Behavior; Social Controls; Social Hierarchy; Social isolation; System; Techniques; Technology; Testing; Thirst; Time; Water; autism spectrum disorder; awake; base; brain health; control theory; deep learning; drinking water; experience; flexibility; genetic technology; imaging study; in vivo; insight; lens; male; millisecond; motivated behavior; negative affect; neural; neural circuit; neuroregulation; novel; optogenetics; physical conditioning; recruit; resilience; social; social contact; social engagement; suicidal behavior; two photon microscopy

PROJECT SUMMARY The importance of social contact for mental and physical health is gaining widespread recognition in the medical and neuroscience communities. Despite the abstract nature of social substrates, there is growing recognition that striking a balance between social contact and isolation, or 'social homeostasis', is critical to mental and physical health. Homeostatic neural control systems have been established for every essential physical resource, including food, water, and body temperature, and act to stabilize internal values around a set point. In contrast, the term 'social homeostasis' has only recently appeared as a conceptual placeholder and no neural control system for social homeostasis has been identified. Intriguingly, a common feature of autism spectrum disorder, in addition to social disruption, is atypical homeostatic behavior―including problems sleeping, unsual eating, excessive water drinking, and hyper or hypo thermal sensitivities. However, it remains unclear whether the neural circuits that regulate social and physical forms of homeostasis are separate or overlapping. Without this information, we are unlikely to understand the complex ways that social contact mediates brain health and disease. Here, we propose to bridge this gap by establishing a new framework of ‘social homeostasis’ in which abstract social substrates are made concrete in terms of identified neural circuits. This project will leverage state-of-the-art in vivo circuit technology to study adult male and female mice engaging in ethologically relevant social and nonsocial homeostatic behaviors. Using specialized imaging technology, we will record the activity of hundreds of individual neurons in real-time in awake behaving mice across social and physical homeostatic challenges. This will illuminate the fixed and flexible dynamics of homeostatic control neurons across distinct behavioral states. In addition, we will apply behavioral optogenetics and whole organ clearing techniques, to establish the wiring and functional encoding of brain wide socially engaged homeostatic circuits. If successful, we will uncover a neural control system for social resources―the first homeostatic control system to regulate a non-physical resource. This will provide a new platform to understand the health and stability of individuals, groups, and populations, and change our understanding of how social experience confers resilience or susceptibility to specific disorders, such as autism spectrum disorder and depression.

项目摘要 社会接触对身心健康的重要性在医疗中获得了广泛的认可 和神经科学社区。尽管社会基材具有抽象的性质，但人们的认可越来越大 在社会接触与孤立之间或“社会稳态”之间达到平衡至关重要 身体健康。为每个基本物理建立了稳态神经控制系统 资源，包括食物，水和体温，并采取行动稳定设定点附近的内部值。 对比，“社会稳态”一词直到最近才成为概念占位符，没有神经元 已经确定了社会稳态的控制系统。有趣的是，自闭症谱系的共同特征 除社会干扰外，疾病是非典型的稳态行为 - 包括睡觉的问题 进食，饮水过多以及超级或低温敏感性。但是，尚不清楚是否 调节社会和身体形式稳态的神经回路是分开或重叠的。没有 这些信息，我们不太可能了解社会接触介导大脑健康的复杂方式和 疾病。在这里，我们建议通过建立一个新的“社会稳态”框架来弥合这一差距 从确定的神经回路方面，将哪些抽象的社会基质制成具体。这个项目将 利用最新的体内电路技术来研究成年男性和女性小鼠在伦理上从事。 相关的社会和非社会稳态行为。使用专业成像技术，我们将记录 在社会和身体上，在醒着的行为中，实时的数百个单个神经元的活动 稳态挑战。这将阐明稳态控制神经元的固定和灵活动力 跨越不同的行为状态。此外，我们将应用行为光遗传学和整个器官清除 技术，以建立大脑广泛社会参与的稳态电路的接线和功能编码。 如果成功，我们将发现社会资源的神经控制系统 - 第一个体内稳态控制系统 调节非物理资源。这将提供一个新的平台，以了解 个人，团体和人群，改变我们对社会经验如何承认弹性的理解 或对特定疾病的敏感性，例如自闭症谱系障碍和抑郁症。