Alcantara Ivan C, Li Chia, Gao Claire, Rodriguez González Shakira, Mickelsen Laura E, Papas Brian N, Goldschmidt Abigail I, Cohen Isabel M, Mazzone Christopher M, de Araujo Salgado Isabel, Piñol Ramón A, Xiao Cuiying, Karolczak Eva O, Li Jian-Liang, Cui Guohong, Reitman Marc L, Krashes Michael J
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Department of Neuroscience, Brown University, Providence, RI, USA.
Nature. 2025 Jul 30. doi: 10.1038/s41586-025-09268-5.
Across mammalian species, new mothers undergo behavioural changes to nurture their offspring and meet the caloric demands of milk production. Although many neural circuits underlying feeding and parenting behaviours are well characterized, 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 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 neurons inhibit bombesin receptor subtype 3 (BRS3) neurons in the MPOA (MPOA neurons), which become more active postpartum and govern parenting and satiety. Activation of this ARC-to-MPOA 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.
在所有哺乳动物物种中，新妈妈会经历行为变化来养育后代，并满足产奶的热量需求。尽管许多与进食和养育行为相关的神经回路已得到充分表征，但尚不清楚这些不同的回路在哺乳期是如何相互作用和适应的。在这里，我们对小鼠下丘脑的弓状核（ARC）和内侧视前区（MPOA）进行了转录组分析，以研究其对哺乳和饥饿的反应。此外，我们发现哺乳期小鼠食欲增强伴随着ARC中促进饥饿的刺鼠相关肽（AgRP）神经元（ARC神经元）活性增加。为了评估饥饿驱动力与母性驱动力的强度，我们设计了一种冲突试验，让雌性小鼠在食物源或幼崽及筑巢材料之间做出选择。尽管饥饿的哺乳期母亲将养育后代置于进食之上，但饥饿缩短了哺乳期和未生育雌性小鼠养育行为的持续时间，并打乱了其行为顺序。我们发现ARC神经元会抑制MPOA中的胃泌素释放肽受体亚型3（BRS3）神经元（MPOA神经元），这些神经元在产后变得更加活跃，并控制养育行为和饱腹感。激活这条从ARC到MPOA的神经回路会使行为从养育转向觅食。因此，下丘脑网络受到生理状态的调节，并在相互竞争的动机行为优先级排序过程中发挥拮抗作用。
