Antagonistic Neural Circuits Drive Opposing Behaviors towards the Young in Females

In many species, including mice, females show strikingly different pup-directed behaviors based on their reproductive state1,2. Naive wild female mice often kill pups while lactating females are dedicated to pup caring3,4. The neural mechanisms that mediate infanticide and its switch to maternal behaviors during motherhood remain unclear. Here, based on the hypothesis that maternal and infanticidal behaviors are supported by distinct and competing neural circuits5,6, we used the medial preoptic area (MPOA), a key site for maternal behaviors7-11, as a starting point and identified three MPOA-connected brain regions that drive differential negative pup-directed behaviors. Further functional manipulation and in vivo recording revealed that estrogen receptor alpha (Esr1) expressing cells in the principal nucleus of the bed nucleus of stria terminalis (BNSTprEsr1) are necessary, sufficient, and naturally activated during infanticide in female mice. Furthermore, MPOAEsr1 and BNSTprEsr1 neurons form reciprocal inhibition and change their excitability in opposite directions with reproductive state. The shift in balance between BNSTprEsr1 and MPOAEsr1 cell activity is likely a key mechanism for the behavioral switch during motherhood.