Neural correlates of adversity-overcoming pup rescue behavior in female mice

Rescuing infants under threat is a fundamental parental behavior in mammals. However, the behavioral expression and neural correlates of adversity-overcoming infant rescue in non-parental female individuals remain poorly understood. In this study, we first established a novel pup rescue paradigm with scalable adversity, in which mothers and virgin female mice have to cross a water pool of varying depths (0, 3, or 20 mm) to retrieve pups into the nest. We unexpectedly found that virgin females were less averse to water and retrieved pups faster than mothers. Next, we implemented an additional hurdle by trapping pups into a tube, so that female mice had to cross the pool and open the tubes to rescue pups. The rescuer virgin females in this “trapped pup” rescue task showed increased neuronal activity in the anterior cingulate cortex, lateral septum, anterior commissural nucleus, basolateral amygdala, and dorsal raphe nucleus, compared with non-rescuers. The c-Fos+ cell densities in these regions showed significant negative correlations with the latencies to rescue behaviors suggesting their positive impact on rescue. Given that the virgin females do not have genetic relations to the rescuee pups, our findings provide a basis for further analyses of adversity-overcoming altruistic behavior and its neural correlates.