Neural basis of collective behavior during environmental stress

环境压力下集体行为的神经基础

• 批准号: 10740543
• 负责人: Tara Raam
• 金额: $ 12.2万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-03 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740543
• 关键词: Address; Anatomy; Animals; Automobile Driving; Behavior; Behavioral; Biological; Biological Assay; Brain; Brain region; Buffers; Calcium; Cells; Communication; Complex; Computer Models; Computer Vision Systems; Data; Decision Making; Detection; Disease; Dissection; Emotional; Foundations; Genetic; Health; Hormones; Human; Hypothalamic structure; Image; Impairment; Individual; Investigation; Knock-out; Laboratory Study; Lateral; Literature; Maps; Medial; Mediating; Mental Health; Mental disorders; Mus; Neurodevelopmental Disorder; Neurons; Neuropeptides; Nucleus Accumbens; Oxytocin; Pathway interactions; Personal Satisfaction; Phase; Physiological; Population; Prefrontal Cortex; Problem Solving; Productivity; Publishing; Regulation; Research; Research Personnel; Resource Sharing; Role; Schizophrenia; Shapes; Signal Transduction; Social Behavior; Social Environment; Social Functioning; Social Interaction; Stress; Symptoms; Technical Expertise; Technology; Temperature; Testing; Thalamencephalon; Training; Virus; Work; autism spectrum disorder; behavioral study; cognitive capacity; cold stress; cold temperature; combat; designer receptors exclusively activated by designer drugs; environmental stressor; experimental study; genetic manipulation; in vivo; in vivo imaging; member; neural; neural circuit; neuromechanism; novel; novel strategies; response; self organization; social; social group; statistical and machine learning; stress management; stressor; therapeutically effective; tool; virus genetics

Project Summary Social interactions are critical to the physical and emotional health of a wide variety of species. Perturbations in social functioning, a hallmark symptom of many psychiatric and neurodevelopmental disorders such as autism and schizophrenia, can profoundly impair an individual’s ability to sustain healthy social relations. While a growing body of literature has elucidated neural circuits for dyadic social interactions (interactions between two individuals), our understanding of higher order interactions at the level of larger groups is remarkably weak. Humans and other species organize themselves into social groups, in which the behavior of each individual both contributes to and benefits from the cohesiveness and well-being of the collective. Social groups serve as a context for sharing of resources, buffering of stress, regulation of homeostatic needs, and a reservoir of cognitive capacity to solve problems and respond to environmental challenges. In order to address this gap in the literature, I am using a novel behavioral approach to study how groups of mice self-organize into huddles in response to a cold temperature thermal challenge. Prior studies examining social groups have been limited by lack of technology to track the pose and identity of each mouse over the duration of a session. To address these challenges, I am using novel multi-animal pose estimation tools developed through computer vision to quantitatively identify huddling configurations in groups of four mice. Furthermore, I am combining this automated behavioral tracking with circuit dissection tools to understand which circuits in the brain coordinate huddling in response to thermal challenge. Published work from our lab and others suggests that medial prefrontal cortex (mPFC) is a critical node involved in regulating group level behaviors and inter-brain dynamics across species. However, the contribution of mPFC and its descending projections to group huddling has never been explored. Furthermore, although whole-brain knockout studies have found that the social hormone oxytocin is necessary for huddling in mice, the precise neural circuits that are engaged by oxytocin to promote huddling never been examined. The experiments described in this proposal will fill a critical gap in our understanding of neural mechanisms for collective behavior by performing detailed quantitative behavioral analysis and neural circuit dissection to physiologically observe, computationally model, and functionally manipulate individual descending projections of the dmPFC during huddling. Using an ethologically relevant group behavior, in vivo freely moving calcium imaging, chemogenetic manipulations, and anatomical mapping, the proposed study will test the hypothesis that oxytocin engages discrete, anatomically-defined pathways descending from the dmPFC to promote group huddling. These results will set the foundation for a more incisive analysis of how dmPFC circuits shape social function in both health and disease. In addition, completion of this work will provide critical training in statistical and machine learning approaches to study the behavior and neural dynamics of social groups, which are essential for the candidate to become a successful independent investigator.

项目摘要 社会互动对各种物种的身体和情感健康至关重要。 社会功能紊乱，许多精神和神经发育障碍的标志性症状 例如自闭症和精神分裂症，会严重损害个人维持健康社会关系的能力。 虽然越来越多的文献已经阐明了二元社会互动（互动）的神经回路 两个个体之间），我们对更大群体水平上的高阶相互作用的理解是 非常虚弱人类和其他物种将自己组织成社会群体，在这些群体中， 每个人都对集体的凝聚力和福祉作出贡献，并从中受益。社会 群体作为一种环境，可以共享资源，缓冲压力，调节自我平衡的需要， 解决问题和应对环境挑战的认知能力储备。为了解决 为了填补文献中的这一空白，我正在使用一种新颖的行为方法来研究小鼠群体如何自我组织成 蜷缩在一起以应对寒冷的温度挑战。以前研究社会群体的研究 由于缺乏在会话期间跟踪每个鼠标的姿势和身份的技术而受到限制。到 为了应对这些挑战，我正在使用通过计算机开发的新颖的多动物姿势估计工具， 视觉来定量识别四只小鼠的组中的蜷缩构型。此外，我还结合了 使用回路解剖工具进行自动行为跟踪，以了解大脑中哪些回路协调 蜷缩在一起以应对高温的挑战我们实验室和其他人发表的研究表明， 前额叶皮层（prefrontalcortex，mPFC）是参与调节群体水平行为和脑间动力学的关键节点 跨越物种。然而，mPFC及其下降预测对群体拥挤的贡献从未 被探索。此外，尽管全脑敲除研究发现，社会荷尔蒙催产素 是小鼠蜷缩所必需的，催产素参与的精确神经回路促进了蜷缩 从未被检查过。本提案中所描述的实验将填补我们理解的一个关键空白， 通过进行详细的定量行为分析和神经机制的集体行为 电路解剖，以生理观察，计算模型，并在功能上操纵个人 下丘脑前额叶皮层的下降投射使用行为学相关的群体行为，在体内 自由移动钙成像，化学遗传学操作和解剖标测，拟议的研究将 检验催产素参与从dmPFC下行的离散的、解剖学定义的通路的假设 来促进群体聚集。这些结果将为更深入地分析dmPFC如何 回路塑造了健康和疾病中的社会功能。此外，这项工作的完成将提供关键的 培训统计和机器学习方法，以研究社会行为和神经动力学 这对候选人成为一名成功的独立调查员至关重要。