What's going on in the brain that can induce aggressive social behavior? This team from the Duke-NUS School of Medicine (Singapore) deciphers, in the Proceedings of the American Academy of Sciences (PNAS), the signaling mechanism that determines social behavior, with implications for understanding the hierarchy social, domination and intimidation, and aggression.
Singapore researchers have found that a growth factor protein called brain-derived neurotrophic factor (BDNF) and its receptor, the tropomyosin receptor kinase B (tropomyosin receptor kinase B or TrkB) influence social dominance, here in mice. This research, certainly on animals, has implications for understanding the neurobiology of aggression and intimidation. "Because rodents like humans are 'social animals'. Each of our interactions follows rules according to a social hierarchy. Failure to adhere to this hierarchy can be detrimental,” comments lead author Prof. Hyunsoo Shawn Je of the Neuroscience and Behavioral Disorders Research Program at Duke-NUS Medical School.
Overriding these hierarchies can lead to problems or responses such as aggression and intimidation. Two behaviors that have a high social cost, which is why a better understanding of their biological causes is a step forward towards better prevention and even effective treatment.
Activity in the brain is mediated by circuits consisting of excitatory neurons, which increase activity, and GABA-ergic interneurons, which inhibit and slow down excitatory activity. Previous studies have shown that BDNF-TrkB signaling is important for the maturation of GABA-ergic interneurons and the development of neural circuits in the brain. However, until this study, the behavioral consequences of disruption of BDNF-TrkB signaling remained unknown.
Loss of BDNF-TrkB pathway and propensity to aggression:the team generated transgenic mice in which the TrkB receptor was knocked out specifically in GABAergic interneurons located in the area of the brain regulating emotional and social behavior, called the cortico-limbic system. The transgenic mice exhibited unusual aggressive behavior when brought into contact with normal mice. To understand the origin of this behavior, the team performed behavioral tests. The team thus finds that the mice are not aggressive to protect their territory but due to an increased struggle for dominance over the other mice in the group. Moreover, these transgenic mice are also injured more than other mice during situations of aggression.
Loss or silencing of the BDNF-TrkB pathway induces reduced inhibition of surrounding excitatory cells by GABA-ergic interneurons and when researchers "switch off" excitatory neurons in a specific area of the brain of transgenic mice, they then restore the excitatory/inhibitory balance and instantly suppress abnormal social dominance behavior.
The study demonstrates that genetic and biological factors can play an unexpected role in social behavior and therefore designates new targets for the prevention or even management of aggressive behavior.