美国国立卫生研究院Michael J. Krashes小组近日取得一项新成果。经过不懈努力，他们开发出调节喂养和养育行为的下丘脑回路。2025年7月30日，国际知名学术期刊《自然》发表了这一成果。

本研究对哺乳期和饥饿期下丘脑弧形核（ARC）和内侧视前区（MPOA）进行了转录组学分析。

此外，研究人员发现，哺乳小鼠的食欲升高伴随着ARC （ARC^AgRP神经元）中促进食欲的（AgRP）神经元活性的增加。为了评估饥饿对母性驱动的强度，课题组设计了一个冲突实验，让雌性老鼠在食物或幼崽和筑巢材料之间做出选择。虽然缺乏食物的哺乳期母亲优先考虑育儿而不是喂养，但饥饿减少了哺乳和处女雌性的育儿行为的持续时间，并扰乱了育儿行为的顺序。课题组发现ARC^AgRP神经元抑制MPOA （MPOA^BRS3神经元）产后活性增强的BRS3神经元，MPOA在产后变得更加活跃，并控制养育和饱腹感。ARC^AgRP到MPOA^BRS3回路的激活将行为从养育子女转变为寻找食物。因此，下丘脑网络受到生理状态的调节，并在竞争动机行为的优先化过程中起拮抗作用。

据了解，在所有哺乳动物物种中，新妈妈都会经历行为上的改变，以哺育它们的后代，并满足产奶所需的热量。尽管哺乳动物喂养和养育行为背后的许多神经回路已经被很好地描述了，但尚不清楚这些不同回路在哺乳期是如何相互作用和适应的。

附：英文原文

Title: A hypothalamic circuit that modulates feeding and parenting behaviours

Author: Alcantara, Ivan C., Li, Chia, Gao, Claire, Rodriguez Gonzlez, Shakira, Mickelsen, Laura E., Papas, Brian N., Goldschmidt, Abigail I., Cohen, Isabel M., Mazzone, Christopher M., de Araujo Salgado, Isabel, Piol, Ramn A., Xiao, Cuiying, Karolczak, Eva O., Li, Jian-Liang, Cui, Guohong, Reitman, Marc L., Krashes, Michael J.

Issue&Volume: 2025-07-30

Abstract: 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.

DOI: 10.1038/s41586-025-09268-5

Source: https://www.nature.com/articles/s41586-025-09268-5