Grant: Discovery Grants Program - Individual

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.