Wu Kaibin, Tang Peiwen, Wang Yuwei, Mai Fangcai, Pan Yidi, Zhang Li I, Tao Huizhong W, Liang Feixue
School of Biomedical Engineering, Southern Medical University, Guangzhou, China.
Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, China.
Nat Commun. 2025 Aug 18;16(1):7664. doi: 10.1038/s41467-025-63062-5.
Maternal defense, a hallmark of motherhood, often involves protecting offspring at personal risk. However, the neural mechanisms underlying the emergence and modulation of this behavior remain not-well understood. Here, we introduce a novel paradigm in which mother mice under threat prioritize offspring protection over self-preservation by approaching, collecting, and retreating pups to safety, a risk-associated behavior that also develops in virgin females following maternal experience. Microendoscopic calcium imaging reveals sequential activation of distinct corticofugal neuronal populations in the medial prefrontal cortex (mPFC) during maternal defense. Specifically, layer (L)6 dopamine receptor D1-expressing (D1) neurons are active during pup approach, while L5 neurons are engaged during pup collection and retreat. Activation of the L6 neurons bidirectionally modulates maternal defense via projections to the medial preoptic area. These findings suggest that mPFC L6 D1 neurons may facilitate the transition to maternal behavior by influencing behavioral selection and initiating maternal defense response under threat.
母性防御是母性的一个标志，通常涉及到以个人风险为代价保护后代。然而，这种行为出现和调节的神经机制仍未得到充分理解。在这里，我们引入了一种新的范式，即处于威胁下的母鼠会通过接近、收集幼崽并将其转移到安全地带，将后代保护置于自我保护之上，这种与风险相关的行为在有过母性经历的处女雌鼠中也会出现。显微内窥镜钙成像显示，在母性防御过程中，内侧前额叶皮质（mPFC）中不同的皮质下行神经元群体会依次被激活。具体而言，表达多巴胺受体D1（D1）的第6层（L6）神经元在接近幼崽时活跃，而L5神经元在收集和转移幼崽时被激活。L6神经元的激活通过投射到内侧视前区双向调节母性防御。这些发现表明，mPFC L6 D1神经元可能通过影响行为选择和在威胁下启动母性防御反应，促进向母性行为的转变。
