Urocortin-3 neurons in the perifornical area mediate the impact of chronic stress on female infant-directed behavior

Infant avoidance and aggression are promoted by activation of the Urocortin-3 expressing neurons of the perifornical area of hypothalamus (PeFA Ucn3 ) in male and female mice. PeFA Ucn3 neurons have been implicated in stress, and stress is known to reduce maternal behavior. We asked how chronic restraint stress (CRS) affects infant-directed behavior in virgin and lactating females and what role PeFA Ucn3 neurons play in this process. Here we show that infant-directed behavior increases activity in the PeFA Ucn3 neurons in virgin and lactating females. Chemogenetic inhibition of PeFA Ucn3 neurons facilitates pup retrieval in virgin females. CRS reduces pup retrieval in virgin females and increases activity of PeFA Ucn3 neurons but does not affect maternal behavior in mothers. Inhibition of PeFA Ucn3 neurons blocks stress-induced deficits in pup-directed behavior in virgin females. Together, these data illustrate the critical role for PeFA Ucn3 neuronal activity in mediating the impact of chronic stress on female infant-directed behavior. Significance statement While a large body of research has studied the impact of maternal stress on offspring, few studies have focused on the neural circuitry underlying reduced maternal behavior in stressed mothers. In this study, we examine the neural substrates involved in reduced infant-directed behavior caused by chronic stress. We find that perifornical area neurons expressing the neuropeptide urocortin-3 are critical mediators of the impact of stress on infant-directed behavior in females.