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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.

项目摘要/摘要社会互动，即两个或更多个人之间的互惠互动，对身体以及各种各样物种的情绪健康。社会功能紊乱，这是许多精神和神经发育障碍，如自闭症和精神分裂症，可能会严重损害个人维持健康社会关系的能力。然而，尽管可能会出现社交行为的中断作为这种障碍的一种症状，消极的社会经历，如暴露在敌对或优势的环境中社会代理人，也可以支持精神障碍的发展和维持，如抑郁症和焦虑。此外，社会互动中支配行为的表达与啮齿动物和人类对精神疾病的恢复力--声称占优势的个体对类似抑郁的症状有弹性，而表现出从属行为的人更容易受到伤害对压力的衰弱作用。尽管越来越多的证据表明，社会支配地位在精神障碍的病因学，我们目前对神经回路机制的理解主导和从属行为仍然非常弱。我们实验室和其他实验室发表的研究成果确定背内侧前额叶皮质(DmPFC)是优势表达的关键节点啮齿动物和人类的行为。然而，dmPFC中的神经计算如何协调社会支配地位的决定被传递到皮质下的边缘区域，从来没有被探索过。这些实验将填补我们对支配的神经机制理解上的一个重要空白通过执行详细的神经回路解剖策略来解剖映射、生理观察、对社交期间dmPFC的个体下行投影进行计算建模和功能操作支配行为。具体地说，概述的建议将1)利用体内光遗传学双向在社会支配行为中操纵dmPFC投射和2)利用体内自由移动的钙成像以光学记录在优势决策期间由投影定义的dmFPC种群。建议数研究将揭示离散的、解剖学上定义的从dmPFC下行的通路是如何在社会支配地位。这些结果将为更深入地分析dmPFC电路的形状奠定基础在健康和疾病方面的社会功能。