Establishing Neural Control Systems for Social Homeostasis

建立社会稳态的神经控制系统

基本信息

批准号：
10435589
负责人：
Jenna Ann McHenry
金额：
$ 62.09万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
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/10435589
关键词：
Address Adult Animals Autonomic nervous system disorders Behavior Behavior Control Behavioral Biological Body Temperature Brain Brain Diseases Brain Mapping Calcium Cardiac Caring Cells Cognitive Communities Complex Confusion Data Disease Eating Elements Emotional Equilibrium Event Experimental Models Female Food Foundations Genetic Genetic Recombination Head Health Homeostasis Human Hunger Hypothalamic structure Image Imaging technology Immune Immune System Diseases Impairment Individual Individual Differences Insecta Lead Link Literature Location Loneliness Medial Mediating Medical Mental Depression Mental Health Metabolic Metabolic Diseases Methodology Modeling Mood Disorders Mus Nature Neurons Neurosciences Organ Partner in relationship Pathologic Phenotype Physiological Play Population Population Dynamics Positioning Attribute Positive Valence Predisposition 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 circuit neuroregulation novel optogenetics physical conditioning premature recruit relating to nervous system resilience social social contact suicidal behavior two photon microscopy

项目摘要

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.

项目概要社会接触对于身心健康的重要性正在获得医学界的广泛认可尽管社会基础具有抽象性，但人们越来越认识到这一点。在社会接触和孤立之间取得平衡，或“社会稳态”，对于精神和心理至关重要身体平衡神经控制系统已针对每项基本的身体健康建立。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。相比之下，“社会稳态”一词最近才作为概念占位符出现，并且没有神经元有趣的是，自闭症谱系的一个共同特征已经被确定。除了社会混乱之外，紊乱也是一种非典型的稳态行为，包括睡眠问题、不寻常的问题饮食、过量饮水以及对温度过高或过低的敏感性，但目前尚不清楚是否会出现这种情况。调节社会和身体稳态的神经回路是独立的或重叠的。这些信息，我们不太可能理解社会接触调节大脑健康的复杂方式在这里，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。该项目将通过已识别的神经回路将抽象的社会基础具体化。利用最先进的体内电路技术来研究成年雄性和雌性小鼠的道德行为使用专门的成像技术，我们将记录相关的社会和非社会稳态行为。在清醒行为的小鼠中，数百个单个神经元在社交和身体方面的实时活动这将阐明稳态控制神经元的固定和灵活动力学。此外，我们将应用行为光遗传学和整个器官清除。技术，建立大脑广泛的社会参与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——第一个稳态控制系统监管非物理资源，这将为了解健康和稳定性提供一个新的平台。个人、群体和人群，改变我们对社会经验如何赋予复原力的理解或对特定疾病的易感性，例如自闭症谱系障碍和抑郁症。