In a study published this week in PNAS, researchers have discovered that a certain growth factor protein and its receptor affect social dominance in mice. The research has implications for understanding the neurobiology of aggression and bullying.
"Humans and rodents are social animals. Our every interaction follows rules according to a social hierarchy. Failure to navigate this hierarchy can be detrimental," explains senior author Hyunsoo Shawn Je from Duke–NUS Medical School. "Our paper may be the first to demonstrate that specific molecular signalling pathways in specialised nerve cells, in a particular location in the brain, are important for the balanced navigation of social hierarchies."
Difficulties in navigating these hierarchies can lead to problems like aggression and bullying. "Given the heavy societal cost of bullying and aggression, understanding the biological causes is a step towards their effective prevention and treatment," Je adds.
Activity within the brain is mediated by circuits made up of excitatory neurons and GABAergic inhibitory interneurons. Previous studies have shown that BDNF–TrkB signaling is important for the maturation of GABAergic interneurons and the development of nerve circuits in the brain. But researchers have not been able to pinpoint the behavioral consequences of disrupted BDNF–TrkB signaling.
Je's team generated transgenic mice in which the TrkB receptor was removed specifically from the GABAergic interneurons in the corticolimbic system—the area of the brain regulating emotional and social behavior. The transgenic mice exhibited unusual aggressive behavior when housed together with normal mice. To understand the origin of this behavior, the team conducted behavioral tests. According to the researchers, the mice were not aggressive because they wanted to defend their territory or because they were stronger. Instead, they fought for status and dominance over other mice in the group.
At the cellular level, the loss of BDNF–TrkB GABAergic interneurons in these transgenic mice resulted in weaker inhibition to surrounding excitatory cells, which became overactive. The team proceeded to optogenetically shut down certain excitatory neurons in the same mice, which reestablished the excitatory/inhibitory balance and, according to first author Shawn Pang Hao Tan, “instantaneously reversed the abnormal social dominance.”