Neural Circuit Dissection of Prefrontal Cortex Projections in Social Dominance Behavior

项目总结/摘要 社会互动，两个或多个个体之间的相互作用，对身体至关重要。 和情绪健康的关系。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， 个人维持健康社会关系的能力。然而，虽然社会行为的破坏可能会出现， 作为这种疾病的症状，负面的社会经历，如暴露于对抗性或支配性的环境， 社会代理人，也可以支持发展和维持精神疾病，如抑郁症 和焦虑此外，在社会交往中，支配行为的表达与 啮齿动物和人类对精神疾病的适应力--那些声称占主导地位的个体 对抑郁样症状有弹性，而表现出从属行为的人更容易受到伤害 压力的衰弱效应。尽管有越来越多的证据表明，社会支配地位在 精神疾病的病因学，我们目前对促进神经回路机制的理解， 支配和从属行为仍然非常薄弱。我们实验室和其他人发表的研究成果 确定了背内侧前额叶皮层（dmPFC）作为表达优势的关键节点 在啮齿类动物和人类中的行为。然而，dmPFC中的神经计算如何协调社交活动， 支配决策被传递到皮层下边缘区域的机制从未被探索过。实验 这一提议中所描述的将填补我们对支配的神经机制的理解中的一个关键空白 行为通过执行详细的神经回路解剖策略来解剖映射，生理观察， 计算模型，并在功能上操纵个人的下降预测的dmPFC在社会 支配行为具体地，所概述的提议将1）利用体内光遗传学来双向地 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 成像以光学记录显性决策期间投影定义的dmFPC群体。拟议 一项研究将揭示，从dmPFC下行的离散的、解剖学定义的通路在 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 在健康和疾病中的社会功能。

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.