Male and female mice both prefer social interaction with female mice under normal conditions, but both switch to preferring males when their survival is threatened, according to a new study by Anqi Wei and colleagues. These preferences are mediated by different neuronal circuitry in male and female mice related to dopaminergic neurons in the brain’s ventral tegmental area, the researchers found. The findings offer a clearer picture of the underlying biology of socio-sexual preferences. These preferences are essential for successful reproduction, but also play a significant role in protective and supportive behaviors that are vital for health and survival among mammals. The researchers examined how socio-sexual preferences can be altered by comparing how mice interacted with and without the presence of trimethylthiazoline, a potent smell that mice respond to as a survival threat. In male mice, neuronal projections from the ventral tegmental area go to the brain’s nucleus accumbens to mediate female socio-sexual preference, but to the medial preoptic area to mediate male preference. In female mice, the firing pattern of neuronal projections from the ventral tegmental area to the nucleus accumbens mediates the switch to preferring male companions under survival stress. Bitna Joo and Kay M. Tye discuss these results in a related Perspective.