Neural Circuit Dissection of Prefrontal Cortex Projections in Social Dominance Behavior

社会支配行为中前额叶皮层投射的神经回路解剖

基本信息

批准号：
10349471
负责人：
Tara Raam
金额：
$ 6.98万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10349471
关键词：
Acute Address Aggressive behavior Anatomy Animal Model Animals Anxiety Behavior Behavioral Biological Assay Brain Calcium Characteristics Complex Computer Models Data Development Disease Dissection Distress Emotional Environment Etiology Event Exposure to Foundations Health Human Image Impairment Individual Laboratories Light Link Maintenance Maps Mental Depression Mental Health Mental disorders Mus Neurodevelopmental Disorder Neurons Nucleus Accumbens Optics Output Pathway interactions Physiological Play Population Population Projection Prefrontal Cortex Publishing Regulation Research Resources Rodent Role Schizophrenia Shapes Signal Transduction Social Behavior Social Dominance Social Functioning Social Hierarchy Social Interaction Spottings Stress Symptoms Testing Tube Work autism spectrum disorder depressive symptoms dorsal raphe nucleus experience experimental study hippocampal pyramidal neuron in vivo in vivo calcium imaging neural circuit neuromechanism novel optical imaging optogenetics prevent relating to nervous system resilience social social defeat social structure therapeutically effective tool

项目摘要

Project Summary/Abstract Social interactions, reciprocal interactions between two or more individuals, 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. However, while disruption in social behavior can arise as a symptom of such disorders, negative social experiences, such as exposure to antagonistic or dominant social agents, can also support the development and maintenance of psychiatric disorders, such as depression and anxiety. Furthermore, expression of dominance behavior during social interactions is strongly linked to resilience to psychiatric disorders in both rodents and humans—individuals who assert dominance are more resilient to depressive-like symptoms, while individuals who display subordinate behaviors are more vulnerable to the debilitating effects of stress. Despite growing evidence of the role that social dominance plays in the etiology of psychiatric disorders, our current understanding of the neural circuit mechanisms that promote dominant and subordinate behaviors remains remarkably weak. Published work from our lab and others has identified the dorsomedial prefrontal cortex (dmPFC) as a critical node for the expression of dominance behaviors in both rodents and humans. However, how neural computations in the dmPFC that orchestrate social dominance decisions are relayed to subcortical limbic regions has never been explored. The experiments described in this proposal will fill a critical gap in our understanding of neural mechanisms for dominance behavior by performing detailed neural circuit dissection strategies to anatomically map, physiologically observe, computationally model, and functionally manipulate individual descending projections of the dmPFC during social dominance behaviors. Specifically, the outlined proposal will 1) utilize in vivo optogenetics to bidirectionally manipulate dmPFC projections during social dominance behaviors and 2) utilize in vivo freely moving calcium imaging to optically record projection-defined dmFPC populations during dominance decisions. The proposed study will reveal how discrete, anatomically-defined pathways descending from the dmPFC are engaged during social dominance. These results will set the foundation for a more incisive analysis of how dmPFC circuits shape social function in both health and disease.

项目概要/摘要社交互动，即两个或更多个人之间的相互互动，对于身体健康至关重要各种物种的社会功能和情绪健康受到干扰，这是一种标志性症状。许多精神和神经发育障碍，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然而，社会行为可能会受到干扰。作为此类疾病的症状，负面的社会经历，例如暴露于敌对或主导的环境中社会因素，还可以支持精神疾病的发展和维持，例如抑郁症此外，社交互动中的支配行为的表达与焦虑密切相关。啮齿类动物和人类对精神疾病的恢复能力——主张统治地位的个体更容易对抑郁样症状有抵抗力，而表现出从属行为的人更容易受到伤害尽管越来越多的证据表明社会主导地位在压力中发挥着重要作用。精神疾病的病因学，我们目前对促进精神疾病的神经回路机制的理解我们实验室和其他人发表的研究成果表明，主导行为和从属行为仍然异常薄弱。确定背内侧前额叶皮层（dmPFC）是表达优势的关键节点然而，dmPFC 中的神经计算如何协调社交行为。支配决策被传递到皮层下边缘区域这一实验从未被探索过。该提案中描述的内容将填补我们对支配神经机制理解的一个关键空白通过执行详细的神经回路解剖策略来解剖学映射、生理学观察、计算模型，并在社交过程中功能性地操纵个体 dmPFC 的下降预测具体来说，概述的建议将 1）利用体内光遗传学进行双向。在社会支配行为期间操纵 dmPFC 预测，2) 利用体内自由移动的钙在优势决策期间光学记录投影定义的 dmFPC 群体的成像。研究将揭示从 dmPFC 下降的离散的、解剖学定义的通路在这些结果将为更深入地分析 dmPFC 电路如何形成奠定基础。健康和疾病中的社会功能。