Urocortin-3 neurons in the perifornical area are critical mediators 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, while CRS does not affect maternal behavior in lactating females. 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.