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一条调节进食和育儿行为的下丘脑回路。

A Hypothalamic Circuit that Modulates Feeding and Parenting Behaviors.

作者信息

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

机构信息

Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA 20892.

Department of Neuroscience, Brown University, Providence, RI, USA 20912.

出版信息

bioRxiv. 2024 Jul 23:2024.07.22.604437. doi: 10.1101/2024.07.22.604437.

Abstract

Across mammalian species, new mothers undergo considerable behavioral changes to nurture their offspring and meet the caloric demands of milk production. While many neural circuits underlying feeding and parenting behaviors are well characterized, it is unclear how these different circuits interact and adapt during lactation. Here, we characterized the transcriptomic changes in 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. To assess the strength of hunger versus maternal drives, we designed a conflict assay where female mice chose between a food source or a chamber containing pups and nesting material. Although food-deprived lactating mothers prioritized parenting over feeding, hunger reduced the duration and disrupted the sequences of parenting behaviors in both lactating and virgin females. We discovered that ARC neurons directly inhibit bombesin receptor subtype-3 (BRS3) neurons in the MPOA, a population that governs both parenting and satiety. Selective activation of this ARC to MPOA circuit shifted behaviors from parenting to food-seeking. Thus, hypothalamic networks are modulated by physiological states and work antagonistically during the prioritization of competing motivated behaviors.

摘要

在哺乳动物物种中,新妈妈会经历相当大的行为变化来养育后代并满足产奶的热量需求。虽然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如何相互作用和适应。在这里,我们描述了小鼠下丘脑弓状核(ARC)和内侧视前区(MPOA)对哺乳和饥饿的转录组变化。此外,我们表明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)神经元活动增加。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装有幼崽和筑巢材料的笼子之间进行选择。尽管饥饿的哺乳期母亲将养育后代置于进食之上,但饥饿减少了哺乳期和未生育雌性的养育行为持续时间并打乱了养育行为的顺序。我们发现ARC神经元直接抑制MPOA中的促胃液素释放肽受体亚型3(BRS3)神经元,这一群体会同时调节养育行为和饱腹感。从ARC到MPOA回路的选择性激活将行为从养育转变为觅食。因此,下丘脑网络受生理状态调节,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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e16/11291030/2f4a7a8f2fd6/nihpp-2024.07.22.604437v1-f0007.jpg

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