The neural mechanisms supporting the rise and fall of maternal aggression

Abstract

To protect the helpless young, lactating females dramatically increase aggression towards intruders, known as maternal aggression. However, attack is costly and risky. When pups no longer exist, maternal aggression rapidly declines. Our study reveals the critical role of the pathway from posterior amygdala cells expressing estrogen receptor alpha (PAEsr1) to the ventrolateral part of ventromedial hypothalamus cells expressing neuropeptide Y receptor Y2 (VMHvlNpy2r) in the rise and fall of maternal aggression. Functional manipulations and recordings demonstrate that VMHvl-projecting PAEsr1 (PAEsr1[->]VMHvl) cells are naturally active and required for maternal aggression. During lactation, PA-VMHvlNpy2r connection strengthens, and VMHvlNpy2r excitability increases to facilitate attack. Furthermore, PAEsr1 expresses abundant oxytocin receptors, enabling oxytocin to boost PAEsr1 cell output. After pup separation, the oxytocin level drops, causing decreased maternal aggression, which can be restored by optogenetically increasing the oxytocin level. Thus, diverse forms of plasticity occur at the PAEsr1-VMHvlNpy2r circuit to support need-based maternal aggression.