CCK中间神经元中的Neuroligin1通过雄性小鼠海马CA2中的去抑制微电路来控制社会记忆的形成
Neuroligin1 in CCK-interneurons gates social memory formation via a disinhibitory microcircuit in the hippocampal CA2 in male mice.
摘要(中文译文)
社会记忆对日常生活至关重要，其受损与精神疾病相关。海马背侧CA2（dCA2）区域已知支持社会记忆的形成，但其如何处理社会信息仍不清楚。本研究表明，在雄性小鼠中，dCA2区域一群特定的神经元——胆囊收缩素阳性中间神经元（CCK-INs）——充当接收社会线索并激活dCA2锥体神经元（PyNs）的枢纽。在社会接触时，CCK-INs被激活，并通过GABA受体抑制小清蛋白阳性中间神经元（PV-INs），从而使PyNs摆脱抑制。从CCK-INs中去除Neuroligin 1（一种与自闭症相关的蛋白）会破坏其功能并导致社会记忆缺陷。重要的是，dCA2的CCK-INs接受来自内侧隔核的直接谷氨酸能输入，而对这些CCK-INs进行化学遗传学激活可挽救由隔核抑制引起的记忆缺陷。这些发现阐明了社会记忆的重要环路机制，并突出了潜在的治疗靶点。
Abstract
Social memory is essential for daily life, and its impairment is associated with psychiatric disorders. The dorsal CA2 (dCA2) region of the hippocampus is known to support social memory formation, yet how it processes social information remains unclear. Here we show that, in male mice, a specific group of dCA2 neurons-cholecystokinin-positive interneurons (CCK-INs)-acts as a hub that receives social cues and activates dCA2 pyramidal neurons (PyNs). Upon social encounters, CCK-INs are activated and suppress parvalbumin-positive interneurons (PV-INs) via GABA receptors, thereby releasing PyNs from inhibition. The removal of Neuroligin 1, an autism-associated protein, from CCK-INs disrupts their function and leads to social memory deficits. Importantly, dCA2 CCK-INs receive direct glutamatergic inputs from the medial septum, and chemogenetic activation of these CCK-INs rescues memory deficits caused by septal inhibition. These findings delineate a important circuit mechanism for social memory and highlight potential therapeutic targets.
如何引用
AMA
Miao Wu, Zixu Wang, Kun Cao, Chengyan Zhu, Zixuan Wang, Meng Li, et al. Neuroligin1 in CCK-interneurons gates social memory formation via a disinhibitory microcircuit in the hippocampal CA2 in male mice.. Nature communications. 2026; doi:10.1038/s41467-026-73903-6.
APA
Miao Wu, Zixu Wang, Kun Cao, Chengyan Zhu, Zixuan Wang, Meng Li, et al (2026). Neuroligin1 in CCK-interneurons gates social memory formation via a disinhibitory microcircuit in the hippocampal CA2 in male mice.. Nature communications. https://doi.org/10.1038/s41467-026-73903-6
GB/T 7714
Miao Wu, Zixu Wang, Kun Cao, Chengyan Zhu, Zixuan Wang, Meng Li, et al. Neuroligin1 in CCK-interneurons gates social memory formation via a disinhibitory microcircuit in the hippocampal CA2 in male mice.[J]. Nature communications, 2026 doi:10.1038/s41467-026-73903-6.
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