A hypothalamic circuit that modulates feeding and parenting behaviours

Across mammalian species, new mothers undergo behavioural changes to nurture their offspring and meet the caloric demands of milk production^1-5. Although many neural circuits underlying feeding and parenting behaviours are well characterized^6-9, it is unclear how these different circuits interact and adapt during lactation. Here we performed transcriptomic profiling of the arcuate nucleus (ARC) and the medial preoptic area (MPOA) of the mouse hypothalamus in response to lactation and hunger. Furthermore, we showed that heightened appetite in lactating mice was accompanied by increased activity of hunger-promoting agouti-related peptide (AgRP) neurons in the ARC (ARC^AgRP neurons). To assess the strength of hunger versus maternal drives, we designed a conflict assay in which female mice chose between a food source or pups and nesting material. Although food-deprived lactating mothers prioritized parenting over feeding, hunger reduced the duration and disrupted the sequences of parenting behaviours in both lactating and virgin females. We found that ARC^AgRP neurons inhibit bombesin receptor subtype 3 (BRS3) neurons in the MPOA (MPOA^BRS3 neurons), which become more active postpartum and govern parenting and satiety. Activation of this ARC^AgRP-to-MPOA^BRS3 circuit shifted behaviours from parenting to food-seeking. Thus, hypothalamic networks are modulated by physiological states and work antagonistically during the prioritization of competing motivated behaviours.