Three tame silver foxes, three aggressive foxes and three wild foxes offered researchers a small window into how breeding may reshape the brain. In a study published Nov. 2 in the journal Current Biology, scientists found that the tame animals had fewer of a type of neuron linked to aggression in a brain region called the ventromedial hypothalamus.

The finding follows a breeding experiment that began on silver fox farms in Siberia in the late 1950s. Russian geneticists noticed that some foxes were more accepting of human caretakers, while others acted more aggressively. They bred the friendlier foxes with one another. After only six generations, the selected animals were producing litters whose young interacted with people. The tamer foxes also developed traits often seen in domesticated animals, including floppy ears and shorter snouts.

Researchers wanted to learn what changes in the brain might accompany this fast shift in behavior. The ventromedial hypothalamus, a region near the base of the brain, was a useful place to look. Earlier studies had linked it to aggression, and research in mice had identified cell types there involved in aggressive behavior. The area also helps control energy use and plays roles in maternal instincts and social behavior in mice.

Working with scientists from the Russian fox colony, the team examined nine preserved brains: three from foxes bred for tameness, three bred for aggression and three wild foxes. They cut the brains into very thin slices and used a fluorescent technique to identify markers for different cell types in the hypothalamus.

The team focused on neurons that express estrogen receptor alpha. In earlier mouse experiments, researchers used light to activate these neurons, and the mice immediately attacked other mice. The fox study found fewer of these aggression-circuit neurons in the tame foxes than in the aggressive or wild groups. The result points to a brain difference associated with selection for friendliness, though it does not yet explain how breeding produced that difference.

Eirene Markenscoff-Papadimitriou, an assistant professor of molecular biology and genetics at Cornell University and the study’s senior author, said the researchers set out to understand the neurological basis of behavior changes that appeared quickly under selective breeding. The work also offers a way to study how environmental pressures can alter brain structure over relatively short periods.

The next question is why domestication is linked to changes in this brain region. Co-author Anna Kukekova, an associate professor of genomic biology and animal sciences at the University of Illinois Urbana-Champaign, may investigate how mutations in different parts of the fox genome affect the development of these neurons. The study does not settle how tameness emerges, but it gives researchers a specific cell type and brain area to investigate as they trace the path from generations of breeding to friendlier behavior.