New research from the Weizmann Insitute of Science shows that by studying wild mice in near-natural conditions, different strategies used by females and males in forming social hierarchies were revealed.

For animals, including humans, one’s place in the social hierarchy can affect everything, including one’s health and lifespan. Researchers at the Weizmann Institute of Science have now used a naturalistic approach to studying how mice form social hierarchies, and they discovered something unexpected.

Though mouse social interactions have been studied for decades, until recently most of the experiments relied on data from lab mice, which have been bred in metal cages over many generations. As previously shown by Professor Tali Kimchi – from Weizmann’s Brain Sciences Department – and other researchers, such breeding blurs mouse social instincts, leading, for example, to reduced territorial behaviour and social competition. In addition, studies of mouse social interactions have traditionally been conducted solely with males.

In a new study from Kimchi’s lab, led by Dr Noga Zilkha together with Dr Itsik Sofer and Dr Silvia Chuartzman, the researchers “went back to nature”, studying mice that were bred directly from a type of field mouse – the kind that gets into your house and garden – and they observed the behaviour of females, as well as males. The setup in their lab was as similar as possible to a natural space where wild mice typically live, while still allowing the researchers to track their every move inside a large arena, in groups. The initial findings showed that wild females, in particular, acted in ways the female lab mice didn’t. They were aggressive, and they formed hierarchies that seemed to be just as rigid as those of the males.

That’s not to say that males and females used the same tricks to get to the top. As the scientists observed the mice over six days and nights, tracking all the behaviors that indicated social status – from eating and drinking, to chasing and running – the researchers found that males and females formed their hierarchies in different ways. If male hierarchies came together quickly – within about a day – mostly through chasing behaviors and other acts of aggression, females took about four days to sort out which was the dominant female and where the others fell in the ranks.

Wild females acted in ways the female lab mice didn’t. They were aggressive, and they formed hierarchies that seemed to be just as rigid as those of the males

By analysing all of the behaviour that had been observed in the male and female mice, the researchers grouped the animals into personality types. They did so in collaboration with Professor Uri Alon and Dr Avi Mayo of Weizmann’s Molecular Cell Biology Department, who developed an algorithm for evaluating complex biological data sets. Male mice turned out to be typically less social than females, and more likely to exhibit aggression or its opposite – running away and hiding. Females, in contrast, turned out to be complicated creatures, aggressive and yet social; they often engaged in actions that could be thought of as social, such as approaching and letting others approach.

Ultimately, however, the hierarchies of both sexes were clear to all members, those on top, in the middle and at the bottom of “the class”. The scientists termed them “despotic”, as the alpha male or female claimed the right to chase others away from food or preferred nesting sites.

The smell of social rank

While human hierarchies are thought to rely heavily on visual and audio cues, mammals like mice emit pheromones, smell signals that send messages, akin to “feeling” emojis on social media. It stood to reason that pheromones would play a role in hierarchy formation and mouse personalities, but how did that fit in with the whole way in which some get to dominate others?

The researchers used genetic tools to block the ability of the mice to smell the others’ pheromones, and once again observed how their social personas developed in the group settings. Now they found that the social scene was mixed-up: Males and females exhibited both aggressive and socially oriented behaviour. For example, the female mice with impaired pheromone sensing got their hierarchy in order within a day – more like aggressive males than wild females.

Zilkha explained the reason for this: “There are male- and female-typical circuits in the brains of both sexes, but they are suppressed differently in males and females by pheromones from other mice. In males, these suppressed circuits govern parenting behaviour, and in females, they regulate mounting behaviour.”

In other words, the pheromone signals from a mouse’s close social circle shape its typical male or female behaviour, and thus, to some extent, its “personality”.

Male mice, according to the data sets the researchers collected, turned out to be complicated, too. While many studies leave out female mice because of their estrous cycle, on the assumption that these would introduce unnecessary noise into the social behaviour models, it was actually the male mice that showed greater variability in their behaviour patterns.

The scientists say that their study has implications for any research group using mice as models for social behaviour. In particular, if the model is to be useful, it should certainly incorporate both females and males.

Moreover, the relevance of the findings goes beyond the study of mice. Zilkha believes that understanding the social behaviour of mice under ecologically relevant conditions can help unravel some aspects of neurobiological disorders that have a social context, including autism, Alzheimer’s and Parkinson’s. In the future, for instance, mouse models of autism may help researchers develop early tests for the condition.

An example of a dominant wild mouse (marked in yellow) aggressively chasing subordinates