The neural mechanisms supporting the rise and fall of maternal aggression

Maternal aggression enables lactating females to protect their vulnerable young1,2, yet its rapid emergence after birth and swift decline when pups are absent remain poorly understood. Our study reveals the critical role of the pathway from posterior amygdala cells expressing oestrogen receptor alpha (PAEsr1) to the ventrolateral part of ventromedial hypothalamus cells expressing neuropeptide Y receptor 2 (VMHvlNpy2r) in the rise and fall of maternal aggression. Projection-specific manipulations and recordings show that PAEsr1 cells projecting to the VMHvl are naturally active during attack and are required for maternal aggression. During lactation, PA-to-VMHvlNpy2r synapses potentiate and VMHvlNpy2r cell excitability increases, enabling heightened aggression. PAEsr1 neurons express abundant oxytocin receptors, allowing oxytocin to boost PA output; after pup removal, declining oxytocin levels reduce PA drive and dampen maternal aggression, a deficit restored by pup reunion or optogenetic elevation of oxytocin. These findings reveal multiple forms of plasticity in a defined PAEsr1–VMHvlNpy2r circuit that collectively implement the adaptive, need-based control of maternal aggression. In mice, female aggression is governed by an amygdala–to–medial hypothalamus circuit that is strengthened during pregnancy and is dynamically amplified by oxytocin during lactation.