Investigating Orbitofrontal Circuit Mechanisms of Social Rank and Dominance Behavior

研究社会等级和支配行为的眶额环路机制

基本信息

批准号：
10670442
负责人：
Christian Cazares
金额：
$ 7.95万
依托单位：
SALK INSTITUTE FOR BIOLOGICAL STUDIES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-03 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10670442
关键词：
Animals Behavior Behavior Control Behavioral Biological Assay Brain Calcium Classification Code Competitive Behavior Computer Analysis Decision Making Detection Dissection Emotions Ensure Environment Event Future Goals Hypothalamic structure Image Impairment Incidence Individual Investigation Knowledge Lateral Machine Learning Measures Medial Mediating Memory Mental disorders Mentorship Modeling Mus Neurobiology Neurodevelopmental Disorder Neurons Outcome Output Play Population Population Dynamics Prefrontal Cortex Primates Process Property Research Research Proposals Resources Rewards Rodent Role Serotonergic System Serotonin Social Behavior Social Controls Social Dominance Social Environment Social Hierarchy Social Interaction Sorting Source Structure System Techniques Testing Time Training Work behavior influence dorsal raphe nucleus experimental study flexibility in vivo mouse model nerve supply neural neural circuit neuropsychiatric disorder neuroregulation novel optogenetics post-doctoral training response social social competition social deficits success tool translational scientist

项目摘要

Throughout the animal kingdom, social species establish social hierarchies and use social rank to guide the appropriate expression of dominance behaviors that are critical for survival. Neurobiological investigations have identified a key role for medial prefrontal cortex to lateral hypothalamus projection circuits in representing social ranks and mediating the expression of social dominance behaviors. The orbitofrontal cortex (OFC) has also been shown to process social information. OFC processes are thought to be mediated by vast neuromodulatory innervation from subcortical structures known to regulate sociability, such as the dorsal raphe nucleus (DRN). Serotonergic (5-HT) DRN neurons have been identified as a key neural substrate for mediating social interaction behaviors and they provide the majority of serotonergic innervation to the OFC. However, it is unclear whether DRN5-HT-OFC circuits can process social ranking information to influence behaviors dictated by social ranks. Our research proposal aims to characterize the largely unexplored role of OFC in representing social ranks as well as reveal for the first time whether OFC interactions with serotonergic systems regulate the expression of social dominance behaviors during social competition. The central hypothesis of this project is that OFC encodes social ranking information during social competition and that serotonergic input from DRN modulates the expression of dominance behaviors. To test this, this research will use machine learning tools to automatically track and classify social competition behaviors in multiple animals. This research will then characterize behavioral states that are encoded by OFC neurons by measuring population dynamics aligned to classified social competition behaviors. Finally, experiments in this project will activate DRN5-HT-OFC projection terminals and establish how manipulating serotonergic circuit activity changes the expression of social dominance behaviors during social competition. Project findings will establish a novel, circuit-specific mechanism for how the brain processes social ranking information to adjust behavior accordingly during social competition. Developing a better understanding of the neuronal mechanisms governing the appropriate expression of social behaviors will provide great value to clinicians and translational researchers wanting to treat social behavior control deficits observed in psychiatric disease. Execution of this proposal will be made possible by the Tye lab’s expertise in social behaviors and neural circuit dissection as well by expanding upon candidate’s prior training in calcium imaging, optogenetics, and computational analysis.

在整个动物王国中，社会物种建立社会等级制度并利用社会等级来指导对生存至关重要的统治行为的适当表达，神经生物学研究已经确定了内侧前额叶皮层到外侧下丘脑投射回路在代表社会等级和调解方面的关键作用。眶额皮层 (OFC) 也被证明可以处理社会信息，该过程被认为是由已知具有调节作用的皮层下结构的大量神经调节神经支配所介导的。社交性，例如中缝背核 (DRN)，血清素能 (5-HT) DRN 神经元已被确定为介导社交互动行为的关键神经基质，它们为 OFC 提供大部分血清素神经支配，但目前尚不清楚。 DRN5-HT-OFC 电路是否可以处理社会排名信息以影响社会排名决定的行为。我们的研究提案旨在描述 OFC 在代表社会排名方面的尚未探索的作用并揭示。首次研究了 OFC 与血清素能系统的相互作用是否调节了社会竞争期间社会支配行为的表达。该项目的中心假设是 OFC 在社会竞争期间对社会排名信息进行编码，而来自 DRN 的血清素输入调节了支配行为的表达。为了测试这一点，这项研究将使用机器学习工具自动跟踪和分类多种动物的社会竞争行为，然后通过测量与分类的社会竞争行为相一致的群体动态来表征由 OFC 神经元编码的行为状态。该项目将激活 DRN5-HT-OFC 投射终端，并确定操纵 5-羟色胺回路活动如何改变社会竞争期间的社会支配行为的表达。该项目的研究结果将为大脑如何处理社会排名信息建立一种新颖的、特定于回路的机制。在社会竞争期间相应地调整行为。更好地理解控制社会行为适当表达的神经机制将为希望治疗精神疾病中观察到的社会行为控制缺陷的牧师和转化研究人员提供巨大的价值。泰伊实验室在社会行为和神经回路解剖方面的专业知识，以及通过扩展候选人之前在钙成像、光遗传学和计算分析方面的培训，成为可能。