A hypothalamic circuit that modulates feeding and parenting behaviours

Ivan C. Alcantara, Chia Li, Claire Gao, Shakira Rodriguez González, Laura E. Mickelsen, Brian N. Papas, Abigail I. Goldschmidt, Isabel M. Cohen, Christopher M. Mazzone, Isabel Araujo Salgado, Ramón A. Piñol, Cuiying Xiao, Eva O. Karolczak, Jian-Liang Li, Guohong Cui, Marc L. Reitman and Michael J. Krashes ()
Additional contact information
Ivan C. Alcantara: National Institutes of Health
Chia Li: National Institutes of Health
Claire Gao: National Institutes of Health
Shakira Rodriguez González: National Institutes of Health
Laura E. Mickelsen: National Institutes of Health
Brian N. Papas: National Institutes of Health
Abigail I. Goldschmidt: National Institutes of Health
Isabel M. Cohen: National Institutes of Health
Christopher M. Mazzone: National Institutes of Health
Isabel Araujo Salgado: National Institutes of Health
Ramón A. Piñol: National Institutes of Health
Cuiying Xiao: National Institutes of Health
Eva O. Karolczak: National Institutes of Health
Jian-Liang Li: National Institutes of Health
Guohong Cui: National Institutes of Health
Marc L. Reitman: National Institutes of Health
Michael J. Krashes: National Institutes of Health

Nature, 2025, vol. 645, issue 8082, 981-990

Abstract: Abstract Across mammalian species, new mothers undergo behavioural changes to nurture their offspring and meet the caloric demands of milk production1–5. Although many neural circuits underlying feeding and parenting behaviours are well characterized6–9, 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 (ARCAgRP 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 ARCAgRP neurons inhibit bombesin receptor subtype 3 (BRS3) neurons in the MPOA (MPOABRS3 neurons), which become more active postpartum and govern parenting and satiety. Activation of this ARCAgRP-to-MPOABRS3 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.

Date: 2025
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DOI: 10.1038/s41586-025-09268-5

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