Researchers at Cornell University have identified a cellular difference in the brains of domesticated silver foxes that may help explain how selective breeding made them more tolerant of humans. The study, published in Current Biology, compared foxes from tame, aggressive and unselected wild lineages developed through the long-running Siberian silver fox experiment.

The team focused on the ventromedial hypothalamus, or VMH, a brain region involved in several fundamental behaviors, including social defense and aggression. Within its ventrolateral subdivision, tame foxes had fewer neurons expressing estrogen receptor alpha, known as ERα, than aggressive foxes.

This cell type has been associated with attack behavior in mouse studies. Experiments using optogenetic and chemogenetic techniques have shown that activating ERα-positive neurons in the VMH can trigger immediate attacks. The researchers therefore proposed that a reduction in this neuronal population could weaken an important subcortical pathway involved in aggression.

The findings come from the breeding program launched by Soviet geneticist Dmitry Belyaev and his team in the late 1950s. The foxes were selected according to their reactions to human handlers, with the friendliest and least fearful animals used for breeding. Within six generations, the selected line displayed markedly tamer behavior and sought human interaction.

Earlier research on domestication has linked behavioral and physical changes to processes involving neural crest cells and adrenal hormones. However, the neural changes underlying reduced aggression have been less clear. The Cornell study points to a specific hypothalamic cell population as a possible anatomical marker of selection for tameness.

The authors said the result shows that selection for social behavior can be associated with changes in deep brain circuits over relatively short evolutionary periods. They are now examining the genetic and developmental mechanisms that may influence the formation or distribution of ERα-positive neurons in the fox hypothalamus.

The study, titled “Hypothalamic cell-type differences associated with selection for tameness in the silver fox,” was authored by Jared L. Klein, Darya V. Shepeleva, Anastasiya V. Vladimirova, Anastasiya V. Kharlamova, Andrew D. Miller, Anna V. Kukekova and Eirene Markenscoff-Papadimitriou.

Sources: Neuroscience News.