Social dominance: mechanisms of the prefrontal cortex

生活在庞大的社会群体中需要我们履行特定的角色，有些人在他们的社会环境中占主导地位，而另一些人则处于从属地位。我的研究项目侧重于理解在社会等级中处于支配地位的个体的大脑与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群居哺乳动物。我们目前正在研究一种叫做组蛋白去乙酰化酶2 （HDAC2）的蛋白质在显性行为中所起的作用。HDAC2是神经元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皮质中的功能，前额皮质是大脑的一个区域，在产生社会行为方面起着核心作用。******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，这些方面需要占据主导地位。第一个目的是研究前额皮质HDAC2水平是否在决定优势地位中起关键作用。为此，我们将进行一系列实验(1)描述前额皮质HDAC2水平与优势行为之间的关系，(2)测试前额皮质HDAC2水平是否足以决定优势行为，以及(3)评估HDAC2调节是否具体影响优势行为，或者是影响社交能力的一种更普遍的机制。******第二个目标是研究产生社会支配地位的大脑区域网络内的神经活动，并了解HDAC2对该网络活动的影响。我们将(1)确定在支配性和顺从性小鼠中不同募集的前额皮质通路，(2)评估这些通路在支配性行为中何时募集，以及(3)确定激活或沉默这些通路是否可以使小鼠成为支配性或顺从性。我们还将研究HDAC2水平是否直接影响支配期大脑的连通性。******因此，该研究项目采用多学科方法来了解支配行为背后的基本大脑机制。这也将是首次测量HDAC2水平如何影响行为动物的大脑活动网络。这里产生的结果将对研究社会行为、产生社会行为的大脑功能的性别差异以及研究与复杂动机行为相关的神经可塑性或神经通路的研究人员感兴趣。

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.