Findings may offer insight into human social disorders

Like humans, mice live in complex social groups, fighting over territory and mates, and learning when it is safest to avoid certain adversaries. After losing even a brief fight, defeated animals will run away from mice that injured them for weeks, a new study suggests.

Led by researchers at the NYU Grossman School of Medicine, the study, published in Naturereveals that such “withdrawal behavior” is influenced by a distinct area beneath the hypothalamus, a part of the brain that controls hunger, sleep and levels of many hormones.

The team previously discovered that this special region, called the anterior ventrolateral portion of the ventromedial hypothalamus (aVMHvl), helps rodents defend themselves against attacks from bullies. Here, the authors further identified the central role of area in fostering more lasting avoidance after being defeated.

The study showed that when rival mice first encounter each other, olfactory information about the opponents is not strong enough to activate aVMHvl cells and cause a retreat. However, once a fight begins, pain (such as from a bite) triggers the release of oxytocin, the “cuddle hormone.”

Although this signal has long been associated with parenthood and attraction, in this case it binds to oxytocin receptors on aVMHvl cells and signals danger. This process links pain signals to the opponent’s scent, so that the next time the aggressor approaches, its scent alone encourages the intimidated mouse to stay away, the authors explain. the study.

“Our findings provide new insight into how oxytocin in the hypothalamus stimulates learning from traumatic social experiences,” said the study’s lead author, Takuya Osakada, Ph.D. “Although the hormone is often associated with positive behaviors like caregiving, our study highlights its key role in social conflict,” adds Osakada, a postdoctoral researcher in NYU’s departments of psychiatry, neuroscience and physiology. Langone Health.

The study team, while cautioning that mice share much brain chemistry with humans but are not identical, says previous research has shown similar “retreat” behavior after social defeat in mice. many species, including humans. Additionally, previous studies on children have linked the experience of bullying to increased social isolation and school absences.

Osakada notes that although previous research has examined rodents’ behavior over time after suffering repeated defeats, the new study is the first to explore the rapid social learning that occurs immediately after losing a fight.

For the research, the study team observed hundreds of mice exposed to a rival for 10 minutes before being separated. They also measured the animals’ brain activity before and after conflict.

The results showed that 24 hours after losing a single fight, social interaction dropped to just 20% of pre-loss levels. Additionally, the results revealed that pain caused the immediate activation of oxytocin-releasing brain cells located right next to the aVMHvl.

To further examine the role of aVMHvl in social avoidance, the researchers blocked the receptors on these cells from binding to oxytocin. They found that rodents whose oxytocin receptors were blocked were less likely to withdraw from their attacker in subsequent encounters. Meanwhile, when the team artificially activated the aVMHvl cells, the animals remained alone even though they hadn’t lost a fight.

“Now that we have a better understanding of the critical forces behind social avoidance, researchers can begin to explore ways to harness oxytocin to treat disorders that affect social skills, such as autism, anxiety social and attention deficit hyperactivity disorder,” said the study’s lead author. Dayu Lin, Ph.D. Lin is a professor in NYU Langone’s Departments of Psychiatry, Neuroscience, and Physiology, as well as a member of its Neuroscience Institute.

That said, Lin cautions that while the team linked aVMHvl to social avoidance, they found no such link with another behavior exhibited by defeated mice: freezing in the face of conflict. As a result, the researchers say that other brain systems are likely involved in defeat behavior, and that understanding these systems is essential before developing oxytocin-based therapies for human social disorders.

The study team next plans to examine whether the newly discovered aVMHvl mechanism might also be involved in the behaviors that rodents use to establish their social hierarchy under more natural conditions, rather than in the artificial scenario of the initial experiment. .