Establishing Neural Control Systems for Social Homeostasis

项目摘要 社会接触对身心健康的重要性在医学界得到了广泛的认可。 和神经科学社区。尽管社会底层具有抽象的性质， 在社会接触和孤立之间取得平衡，或“社会稳态”，对心理和 身体健康稳态神经控制系统已经建立了每一个基本的物理 它是一种资源，包括食物、水和体温，并在设定点附近稳定内部值。在 相反，“社会内稳态”一词直到最近才作为一个概念占位符出现， 控制系统的社会稳态已经确定。有趣的是，自闭症谱系的一个共同特征 除了社会混乱之外，失调是一种非典型的自我平衡行为，包括睡眠问题， 进食、过度饮水以及热敏感性过高或过低。然而，目前尚不清楚是否 调节社会和身体形式的稳态的神经回路是分开的或重叠的。没有 这些信息，我们不太可能理解社会接触介导大脑健康的复杂方式， 疾病在这里，我们建议通过建立一个新的“社会动态平衡”框架来弥合这一差距， 这些抽象的社会基础通过识别的神经回路变得具体化。该项目将 利用最先进的体内电路技术来研究成年雄性和雌性小鼠在行为学上的行为， 相关的社会和非社会自我平衡行为。利用专门的成像技术，我们将记录下 在清醒的行为小鼠中，数百个单个神经元的实时活动， 自我平衡的挑战这将阐明稳态控制神经元的固定和灵活动态 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，以建立大脑广泛的社会参与稳态电路的布线和功能编码。 如果成功，我们将发现一个社会资源的神经控制系统-第一个自我平衡控制系统 来管理非物质资源。这将提供一个新的平台，以了解健康和稳定的 个人、群体和人口，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。

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.