Introvert or extrovert?

How do genes contribute to specific behaviors, and shape personality? A Weizmann Institute study has both identified four distinct temperaments among mice—comparable to personality characteristics in humans—and linked them to specific genetic profiles, a major step towards enabling scientists to more deeply study mental health and illness in people.

The study was conducted by the lab of Prof. Alon Chen of the Department of Neurobiology and President of the Weizmann Institute, together with colleagues at the Max Planck Institute of Psychiatry in Munich. The study was co-led by Dr. Oren Forkosh and Stoyo Karamihalev in the Chen lab. The findings may have solved one of the chief difficulties facing neuroscientists who rely on preclinical models such as mice to study mental health and illness: the lack of a comprehensive way to assess mouse personality. The results appeared in the November issue of Nature Neuroscience.

“This systematic categorization of individual differences into constituent traits is an essential step towards more targeted explorations of the biology of mental health,” says Prof. Chen.

While human personality can be assessed through written personality tests—think ‘Big Five’ and other multiple-choice tests—mouse personality can only be assessed through exhibited behaviors. (Scientists agree that mice, like infants, don’t really have personalities, but rather temperaments). Humans are tested, for instance, for how they place on the degrees to which they exhibit openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism. In contrast, the Chen lab tested groups of interacting mice for behavioral traits like dominance, curiosity, approachability, and aggressiveness.

City mouse, country mouse

The four personality traits—known scientifically as ‘identity domains’ or IDs—arose from the scientists’ identification 60 different types of behaviors exhibited during hours of video footage that included mice exploring, chasing, fleeing, foraging, eating alone or in groups, and more. While the IDs were left unlabeled intentionally by the researchers—to avoid attributing human characteristics to animals—to the study revealed their impact on various behaviors and properties of the mice. For example, the most prominent temperament correlated strongly with the mouse’s dominance.

Working together with Prof. Uri Alon from the Department of Molecular Cell Biology, the Chen team found that combining information about two of the IDs produced three distinct behavioral archetypes. These archetypes can be broadly categorized as ‘city mice’ (dominant and interactive), ‘country mice’ (isolationist, ultra-dominant) and ‘subordinate mice’. Most mice—like most humans—are a mix of archetypes.

The method is not far off from the way in which human personality tests are assessed on five dimensions—traits that are consistent over time.

Meanwhile, the scientists also showed that the four dimensions corresponded to a variety of differences in gene expression in the mouse brain—showing tangible genetic differences between the groups. This was done using single-cell RNA-sequencing tools and genetically modified mouse strains.

The study represents the first-ever objective and consistent method to assess mouse behavior and the implications for deeper study of human mental health are substantial.

“This method will open doors to all sorts of research,” says Dr. Forkosh, formerly a postdoctoral fellow in the Chen lab and is now a principal investigator at the Hebrew University of Jerusalem. “If we can identify the genetics of personality, we might also be able to diagnose and treat problems when these genes go wrong. We might even, in the future, be able to use these insights to develop more personalized psychiatry.”

Prof. Alon Chen’s research is supported by the Vera and John Schwartz Professorial Chair in Neurobiology; the Ruhman Family Laboratory for Research in the Neurobiology of Stress; the Perlman Family Foundation, founded by Louis L. and Anita M. Perlman; the Fondation Adelis; Bruno Licht; and Sonia T. Marschak.