Understanding your place in social systems not only conserves biological resources, diminishing energy expended in acts of aggression, it could be your key to survival. Earlier studies have linked a highly interconnected region in the frontal lobe of the brain called the medial prefrontal cortex (mPFC) to social dominance in humans and rodents, but the precise mechanisms and circuits are unclear.

In a new study, scientists at the Salk Institute have delved into poorly understood neural correlates of how individuals compute social rank, based on social competition assays and AI models of neural activity recordings conducted on mice.

In addition to a new assay where mice compete for rewards, the researchers developed a digital vision tool called AlphaTracker to track multiple, unmarked animals. Combining a hidden Markov model with linear models, the authors decoded the overall neural activity in the mPFC to predict the behavior of mice in social competition assays in accordance with their social rank. The team revealed a top-down neural circuit involving neurons in the mPFC and the lateral hypothalamus that regulates behaviors of social dominance, specifically in competitive scenarios that involve a reward.

From left: Kanha Batra, Kay Tye and Nancy Padilla-Coreano (Salk Institute)

Kay Tye, PhD, professor at the systems neurobiology laboratory at Salk’s Institute and senior author of the paper said, “Most social species organize themselves into hierarchies that guide each individual’s behavior. Understanding how the brain mediates this may help us understand the interplay between social rank, isolation, and psychiatric diseases, such as depression, anxiety, or even substance abuse.”

The findings were published on March 16, 2022, in the journal Nature, in an article titled “Cortical ensembles orchestrate social competition via hypothalamic outputs.”

The team found patterns of brain activity differ in mice depending on the social rank of an opposing animal. Based on studies correlating brain activity patterns with established social ranks, the scientists accurately predicted which animal would win a food reward.

To develop a natural social hierarchy in a group of mice, the team initially housed four mice in a cage. They then selected pairs from these in a “round robin” style and pitted them against each other to compete for a food reward. The team used new wireless devices to record brain activity in free-roaming animals and developed an AI tracking tool to compute and analyze differences in their behavior using a new modeling approach. The scientists found the activity of neurons in the mPFC of a mouse could predict the rank of its opponent with 90 percent accuracy.

The first author of the paper, Nancy Padilla-Coreano, PhD, who conducted the experiments as a postdoctoral fellow at Salk and is now an assistant professor at the University of Florida was surprised at the results that showed the neural activity in the animals not only signaled social rank at the start of a competition but continuously represented social rank.

Mice that have formed a social hierarchy get placed in a box where they compete for a food reward. Salk scientists can use brain readouts to accurately predict which animal will win the reward and the social rank of the animal (Salk Institute)

The authors found, activity of mPFC neurons was associated with behaviors such as the speed of movement. This allowed them to predict which mouse would win the food reward, even before the competition started. The winner was not always the more dominant mouse, but the one engaged in a “winning mindset.” The model, the authors said, captured competitive success with a high degree of accuracy. The authors found an animal’s confidence and “winning mindset” may decrease in the presence of mouse of a higher social rank.

“This is the first time we’ve been able to capture these internal states that connect social rank to behavior,” said Kanha Batra, a graduate student in Tye’s lab and co-first author of the paper. “At any timepoint, we could predict an animal’s next move from brain activity using these internal states.”

The team also found differences in neural activity in animal engaged in competition versus when they were collecting their reward, as well as when they were in a group versus alone. The team could still decode social rank of animals living in a group from their brain activity when the animals were alone.

“This is all further evidence to suggest that we are in different brain states when we are with others compared to when we’re alone,” said Tye. “Regardless of who you’re with, if you’re aware of other people around you, your brain is using different neurons.”

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