Establishing Neural Control Systems for Social Homeostasis

点击翻译按钮获取中文摘要

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.