上海交通大学医学院徐天乐团队的一项最新研究显示，神经肽Y选择神经元集合来维持记忆的稳定性和稳定性。相关论文于2026年3月31日发表在《自然—神经科学》杂志上。

本研究表明，在接受线索恐惧记忆训练和消退的雄性小鼠中，腹侧CA1 （vCA1）中表达神经肽Y (NPY) (NPY⁺)  GABA-能的中间神经元既能快速抑制 GABA-能促进记忆获得，也能缓慢抑制NPY介导的 GABA-能促进消退。具体来说，NPY⁺神经元的钙动力学和vCA1中NPY的释放随着灭绝学习的进展和行为状态从“恐惧开启”到“恐惧关闭”的转换而增加。该课题组发现，NPY通过作用于两个由NPY受体1 （NPY1R）表达和NPY2R表达神经元组成的非重叠亚群来控制记忆消退的速率和程度，从而分别控制记忆消退的早期快速和晚期缓慢阶段。它们，亚型特异性，中间神经元缓慢的肽能抑制调节印迹不稳定性。

据了解，印痕是由兴奋性主神经元亚群的活动依赖性募集形成的，而抑制性神经元介导记忆的不稳定性和稳定性。特定类型的中间神经元是否优先参与决定记忆的命运仍然是未知的。

附：英文原文

Title: Neuropeptide Y co-opts neuronal ensembles for memory lability and stability

Author: Wu, Yan-Jiao, Gu, Xue, Kong, Yalei, Yang, Shuo, Wang, Huan, Xu, Miao, Wang, Qi, Yi, Xin, Lin, Ze-Jie, Jiao, Zhi-Han, Cheung, Hoiyin, Zhao, Xin-Yu, Bian, Xin, Jiang, Qin, Li, Ying, Zhu, Michael X., Wang, Lu-Yang, Li, Yulong, Huang, Ju, Li, Qian, Li, Wei-Guang, Xu, Tian-Le

Issue&Volume: 2026-03-31

Abstract: Engrams are formed by activity-dependent recruitment of subsets of excitatory principal neurons, whereas inhibitory neurons mediate memory lability and stability. It remains elusive whether specific types of interneurons are preferentially engaged in determining the fate of memory. Here we show, in male mice undergoing cued fear memory training and extinction, that neuropeptide Y (NPY)-expressing (NPY+) GABA-ergic interneurons in ventral CA1 (vCA1) exert both fast GABA-ergic inhibition to facilitate memory acquisition and slow NPY-mediated inhibition to facilitate extinction. Specifically, the calcium dynamics of NPY+ neurons and NPY release in vCA1 ramp up as extinction learning progresses and the behavioral state switches from ‘fear-on’ to ‘fear-off’. We show that NPY is necessary and sufficient to control the rate and degree of memory extinction by acting on two nonoverlapping subensembles composed of NPY receptor 1 (NPY1R)-expressing and NPY2R-expressing neurons, thereby gating early fast and late slow stages of extinction, respectively. Thus, subtype-specific, slow peptidergic inhibition from interneurons regulates engram lability versus stability.

DOI: 10.1038/s41593-026-02235-x

Source: https://www.nature.com/articles/s41593-026-02235-x