A hypothalamic circuit that modulates feeding and parenting behaviours

• 成果类型: Article
• 署名作者: Alcantara, Ivan C.; Li, Chia; Gao, Claire; Rodriguez Gonzalez, Shakira; Mickelsen, Laura E.; Papas, Brian N.; Goldschmidt, Abigail I.; Cohen, Isabel M.; Mazzone, Christopher M.; de Araujo Salgado, Isabel; Pinol, Ramon A.; Xiao, Cuiying; Karolczak, Eva O.; Li, Jian-Liang; Cui, Guohong; Reitman, Marc L.; Krashes, Michael J.
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Brown University; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
• 刊物名称: NATURE
• ISSN/ISSBN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-025-09268-5
• 发表日期: 2025-09-25
• 关键词: medial preoptic area; ventral premammillary nucleus; agouti-related protein; maternal-behavior; arcuate nucleus; neural circuit; neurons; expression; hunger; parallel

摘要

Across mammalian species, new mothers undergo behavioural changes to nurture their offspring and meet the caloric demands of milk production1, 2, 3, 4-5. Although many neural circuits underlying feeding and parenting behaviours are well characterized6, 7, 8-9, 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.