Duke NUS researchers have discovered that a growth factor protein, brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), influence social dominance in mice. Research has an impact on understanding the neurobiology of aggression and bullying.
"Humans and rodents are social animals, each our interaction follows rules according to a social hierarchy, and non-navigating this hierarchy can be harmful." explained senior author A / Prof. Hyunsoo Shawn Je, from the Neuroscience and Behavioral Disorders research program at Duke-NUS Medical School. "Our paper may be the first to show that specific molecular signaling pathways in specialized neurons at a particular location in the brain are important for the balanced control of social hierarchies."
Difficulties navigating these hierarchies can lead to problems such as aggression and bullying. "Given the high societal cost of bullying and aggression, understanding biological causes is a step toward their effective prevention and treatment," A / Prof. Je added.
The activity in the brain is mediated by circuits consisting of excitatory neurons that increase activity and GABA-ergic interneurons that inhibit and calm the excitatory activity. Previous studies have shown that BDNF-TrkB signaling is important for the maturation of GABA-ergic interneurons and the development of nerve circuits in the brain. However, the researchers have failed to determine the behavioral consequences of BDNF-TrkB impaired signaling.
A / Prof Jes team generated transgenic mice in which the TrkB receptor was specifically removed in the brain GABAergic interneurons that regulate the emotional and social behavior known as the corticolimbic system. The transgenic mice showed unusual aggressive behavior when kept together with normal mice. To understand the origin of this behavior, the team conducted behavioral tests. They found that the mice were not aggressive in protecting their territory. Nor were they aggressive because they were stronger; the transgenic mice were injured more in aggression than other mice. Instead, their aggressive behavior was the result of increased struggle for status and dominance over other mice in the group.
The researchers found that GABAergic interneurons in these transgenic mice provided weaker inhibition due to the loss of BDNF-TrkB surrounding stimulating cells that became overactive. They continued to eliminate excitatory neurons in a certain area of the brains of transgenic mice, restoring the "excitatory / inhibitory" balance and "immediately reversing the abnormal social dominance," says Duke-NUS, postdoctoral fellow. Shawn Pang Hao Tan, who was the first author of the article.
A significant amount of research has focused on the role of family and peer networks in aggressive behavior. This study, along with other recently published findings, shows that genetic and biological factors can play an unexpected role in social behaviors, Je said.
https://www.duke-nus.edu.sg/ News / Neurobiology-Social Aggression