Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-Ku, Sendai, 980-8578, Japan.
Nat Commun. 2023 Apr 20;14(1):2105. doi: 10.1038/s41467-023-37736-x.
The ventral hippocampus (vHC) is a core brain region for emotional memory. Here, we examined how the vHC regulates stress susceptibility from the level of gene expression to neuronal population dynamics in male mice. Transcriptome analysis of samples from stress-naïve mice revealed that intrinsic calbindin (Calb1) expression in the vHC is associated with susceptibility to social defeat stress. Mice with Calb1 gene knockdown in the vHC exhibited increased stress resilience and failed to show the increase in the poststress ventral hippocampal sharp wave ripple (SWR) rate. Poststress vHC SWRs triggered synchronous reactivation of stress memory-encoding neuronal ensembles and facilitated information transfer to the amygdala. Suppression of poststress vHC SWRs by real-time feedback stimulation or walking prevented social behavior deficits. Taken together, our results demonstrate that internal reactivation of memories of negative stressful episodes supported by ventral hippocampal SWRs serves as a crucial neurophysiological substrate for determining stress susceptibility.
腹侧海马体（vHC）是情绪记忆的核心脑区。在这里，我们从基因表达水平到神经元群体动力学，研究了 vHC 如何调节雄性小鼠的应激易感性。应激-naive 小鼠样本的转录组分析显示，vHC 中的内在钙结合蛋白 1（Calb1）表达与对社会挫败应激的易感性相关。vHC 中 Calb1 基因敲低的小鼠表现出应激弹性增加，并且未能显示出应激后腹侧海马体尖波涟漪（SWR）率的增加。应激后 vHC 的 SWR 触发应激记忆编码神经元集合的同步再激活，并促进信息传递到杏仁核。实时反馈刺激或行走抑制应激后 vHC 的 SWR 可防止社交行为缺陷。总之，我们的研究结果表明，由腹侧海马体 SWR 支持的对负面应激事件的记忆的内在再激活是决定应激易感性的关键神经生理基础。
