Social dominance: mechanisms of the prefrontal cortex

社会支配地位：前额叶皮层的机制

• 批准号: RGPIN-2017-06490
• 负责人: Franklin, Tamara
• 金额: $ 4.37万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=764309
• 关键词: Social; dominance; mechanisms; prefrontal; cortex

Living in large social groups requires us to fulfill particular roles, with some individuals dominant within their social environment, and others subordinate. My research program is focused on understanding how the brains of dominant individuals differ from the brains of individuals that are subordinate within their social hierarchy. To do this, we use mice, a social mammal that forms complex dominance hierarchies. We are currently investigating the role that a protein, called histone deacetylase 2 (HDAC2), plays in dominance behaviour. HDAC2 is an important regulator of gene expression in neurons and can affect brain activity. We are specifically focusing on its function within the prefrontal cortex, a brain area that plays a central role in generating social behaviours. The current research program has two main aims, each targeting a different aspect of the brain function required to be dominant. The first aim is to investigate whether prefrontal cortical HDAC2 levels are critical in determining dominance. For this, we will perform a number of experiments (1) to describe the association between prefrontal cortical HDAC2 levels and dominance behaviours, (2) to test whether prefrontal HDAC2 levels are sufficient to determine dominance behaviours, and (3) to assess whether HDAC2 regulation affects dominance behaviours specifically, or is a more general mechanism that affects sociability.The second aim is to investigate neural activity within the network of brain regions recruited to generate social dominance, and to understand the impact of HDAC2 on this network activity. We will (1) identify prefrontal cortical pathways that are differentially recruited in dominant and submissive mice, (2) assess when these pathways are recruited during dominance behaviours, and (3) identify whether activating or silencing these pathways can make a mouse dominant or submissive. We will also investigate whether HDAC2 levels directly impact brain connectivity during dominance.This research program therefore uses a multidisciplinary approach to understand the basic brain mechanisms underlying dominance behaviours. It will also be the first to measure how HDAC2 levels affect a network of brain activity in behaving animals. Results generated here will be of interest to researchers studying social behaviours, sex differences in the brain function generating social behaviours, and those studying the neural plasticity or neural pathways related to complex motivated behaviours.

生活在大的社会群体中需要我们扮演特定的角色，一些人在他们的社会环境中占主导地位，而其他人则处于从属地位。我的研究项目集中在理解占主导地位的个体的大脑与社会等级中处于从属地位的个体的大脑有何不同。为了做到这一点，我们使用了老鼠，一种形成复杂统治等级的社会哺乳动物。我们目前正在研究一种名为组蛋白去乙酰化酶2（HDAC2）的蛋白质在显性行为中的作用。HDAC2是神经元中基因表达的重要调节因子，可以影响大脑活动。我们特别关注它在前额叶皮层中的功能，这是一个在产生社会行为中起核心作用的大脑区域。目前的研究计划有两个主要目标，每个目标都针对大脑功能的不同方面。第一个目的是调查是否前额叶皮质HDAC2水平是决定优势的关键。为此，我们将进行许多实验（1）以描述前额叶皮质HDAC 2水平与支配行为之间的关联，（2）以测试前额叶HDAC 2水平是否足以确定支配行为，以及（3）以评估HDAC 2调节是否特别影响支配行为，或者是一种更普遍的影响社交能力的机制。第二个目标是研究大脑区域网络中的神经活动，这些区域被招募来产生社交优势，并了解HDAC2对该网络活动的影响。我们将（1）确定在支配和顺从小鼠中差异招募的前额叶皮层通路，（2）评估这些通路在支配行为期间何时被招募，以及（3）确定激活或沉默这些通路是否可以使小鼠显性或顺从。 我们还将研究HDAC2水平是否直接影响主导期间的大脑连接。因此，本研究计划使用多学科方法来了解主导行为的基本大脑机制。它也将是第一个测量HDAC2水平如何影响行为动物大脑活动网络的方法。这里产生的结果将是感兴趣的研究人员研究社会行为，性别差异的大脑功能产生社会行为，以及那些研究神经可塑性或神经通路相关的复杂的动机行为。