Mouse Brain Cells Activate When They Witness a Fight

EDITOR'S CHOICE IN Neuroscience

Whether it’s a lioness aggressively protecting her cubs or a chimpanzee defending his territory against unfamiliar rivals, life in nature is not always peaceful. The reasons animals clash with each other may vary, but one aspect holds true: Fights are rarely a private affair in the wild. Often, there are spectators.

Nirao Shah and his team at Stanford University wondered how those individuals on the sidelines of a fight perceive aggressive interactions. Their findings, published in Cell, describe a subset of neurons in the hypothalamus that fire when a mouse fights or watches other mice fight, indicating the existence of mirror neurons, cells that are active when an animal performs and observes a behavior. Their results also revealed that these cells trigger aggression, pointing to a functional role of these neurons.

Shah’s team previously identified a cluster of neurons in a brain region called the ventrolateral part of the ventromedial hypothalamus (VMHvl) that triggered aggression in mice. Those findings have been replicated by other researchers over the years, providing strong evidence that the VMHvl is the rage center of the brain. A few years later, though, his team made the surprising observation that stimulating these rage cells in group-housed mice did not induce attacks, suggesting that social context could regulate the activity of these neurons.¹

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Most evidence for this particular nucleus of the hypothalamus is related to the generation of the behavior, not necessarily anything cognitive. And mirror neurons are a cognitive ability.

—Nancy Padilla-Coreano, University of Florida

To investigate this idea, the researchers recorded the activity of the VMHvl cells in mice under two conditions: when they participated in a fight or when they witnessed other mice fight. The team introduced a male mouse into another’s cage to initiate a fight. The resident mouse attacked the intruder and displayed threatening behaviors, such as tail rattling, to defend its territory. To set up an observer, the researchers placed a mouse in an adjacent compartment separated from the fight arena by a transparent divider. The researchers found that the same population of VMHvl neurons that fired when mice fought also activated when they observed others fight, indicating that these cells mirror aggressive behavior.

Next, they wondered whether these neurons trigger aggression. To find out, the team used genetically engineered mice that allowed them to stimulate or inhibit the cells’ firing. “If we silence these neurons, aggression is basically gone, but mating with females is unaffected, [suggesting that] mirroring neurons are required for aggression, but not for another equally important social behavior. When we activate these neurons, males attack other males more viciously. Instead of mating a female, they attack females, and if you give them a mirror, they will attack their own image,” Shah said.

Nancy Padilla-Coreano, a neuroscientist at the University of Florida who was not involved in the study, said that the findings broaden the understanding of the hypothalamus’s function. “Most evidence for this particular nucleus of the hypothalamus is [related to] the generation of the behavior, not necessarily anything cognitive. And mirror neurons are a cognitive ability.”

She also suggested investigating if this phenomenon is sexually dimorphic as a next step. “[Females] are aggressive in certain conditions as opposed to males who seem to need less reason to be aggressive. If the mirror neurons are only in the males, that could suggest that mirror neurons are a function of the higher baseline of aggression.”