Social dominance: mechanisms of the prefrontal cortex

生活在大的社会群体中需要我们履行特定的角色，一些人在他们的社会环境中占主导地位，另一些人则从属于他们。我的研究项目专注于了解主导个人的大脑与在其社会等级中处于从属地位的个人的大脑有何不同。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性哺乳动物。我们目前正在研究一种名为组蛋白脱乙酰酶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叶皮质中的功能，这是一个在产生社会行为方面发挥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一个不同方面，这是占主导地位所必需的。第一个目的是调查前额叶皮质HDAC2水平是否在决定优势中起关键作用。为此，我们将进行一些实验(1)描述前额叶皮质HDAC2水平与优势行为之间的联系，(2)测试前额叶HDAC2水平是否足以决定优势行为，以及(3)评估HDAC2调节是否特定地影响优势行为，或者是影响社交能力的更一般机制。*第二个目标是调查被招募来产生社交优势的大脑区域网络中的神经活动，并了解HDAC2对这一网络活动的影响。我们将(1)确定在优势小鼠和顺从小鼠中差异招募的前额叶皮质通路，(2)评估这些通路在优势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处于优势或顺从状态。我们还将调查HDAC2水平是否直接影响统治期间的大脑连通性。因此，本研究计划使用多学科方法来了解支配行为背后的基本大脑机制。这也将是第一次测量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的研究人员、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.