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.

项目总结 社会交往对身心健康的重要性正得到医学界的广泛认可 和神经科学社区。尽管社会背景具有抽象的性质，但人们越来越多地认识到 在社会接触和孤立之间取得平衡，或者说社会动态平衡，对精神和心理健康至关重要。 身体健康。动态平衡神经控制系统已经为每一种基本的物理 资源，包括食物、水和体温，并采取行动将内部价值稳定在设定点附近。在……里面 相比之下，社会动态平衡这个术语只是最近才出现的一个概念占位符，而不是神经 社会动态平衡的控制系统已经确定。有趣的是，自闭症谱系的一个共同特征 混乱，除了社会混乱之外，还是一种非典型的自我平衡行为--包括睡眠问题、不自觉的 进食、过量饮水以及热敏度过高或过低。然而，目前还不清楚是否 调节社会和物质形式的动态平衡的神经回路是分开的或重叠的。如果没有 这些信息，我们不太可能理解社会接触调节大脑健康和 疾病。在这里，我们建议通过建立一个新的‘社会动态平衡’框架来弥合这一鸿沟 这些抽象的社会基础是根据识别的神经回路而具体化的。这个项目将 利用最先进的体内电路技术研究成年雄性和雌性小鼠在行为学上的行为 相关的社会性和非社会性动态平衡行为。利用专门的成像技术，我们将记录 清醒行为小鼠社会和生理状态下数百个神经元的实时活动 动态平衡挑战。这将阐明动态平衡控制神经元的固定和灵活的动态。 跨越不同的行为状态。此外，我们将应用行为光遗传学和整体器官清除 技术，以建立全脑社会参与的动态平衡电路的连接和功能编码。 如果成功，我们将发现一种社会资源的神经控制系统--第一个自我平衡控制系统 管理一种非物质资源。这将提供一个新的平台来了解健康和稳定的 个人、群体和人群，并改变我们对社会经验如何赋予韧性的理解 或对特定疾病的易感性，如自闭症谱系障碍和抑郁症。