Hypothalamic cell-type differences associated with selection for tameness in the silver fox

The hypothalamus is a highly heterogeneous brain region that regulates fundamental physiological processes and behaviors, including innate social behaviors such as aggression, mating, and parenting¹. Distinct cell types within hypothalamic nuclei have been linked to social behaviors, a principle established most clearly in mice, where manipulation of defined hypothalamic neuronal subtypes can initiate or suppress behaviors including attack, mounting, and parenting^1,2,3,4. Whether hypothalamic cell types are modified as a result of selection during the evolution of social behavior remains unknown. Silver foxes (Vulpes vulpes) have been selectively bred for tame or aggressive behaviors and we have studied whether there are differences relating to these behaviors in the cellular makeup of the hypothalamus. We report here that tame foxes have fewer estrogen receptor-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) than aggressive foxes, and that this reduction is specific to a neuronal subtype linked to aggressive states in mice⁵. We have thus identified a candidate hypothalamic neuronal subtype associated with selection on social behavior during animal domestication.