Epileptogenesis, arising from alterations in synaptic strength, shares mechanistic and phenotypic parallels with memory formation. However, direct evidence supporting the existence of seizure memory remains scarce. Leveraging a conditioned seizure memory (CSM) paradigm, we found that CSM enabled the environmental cue to trigger seizure repetitively, and activating cue-responding engram cells could generate CSM artificially. Moreover, cue exposure initiated an analogous process of memory reconsolidation driven by mammalian target of rapamycin–brain-derived neurotrophic factor signaling. Pharmacological targeting of the mammalian target of rapamycin pathway within a limited time window reduced seizures in animals and interictal epileptiform discharges in patients with refractory seizures. Our findings reveal a causal link between seizure memory engrams and seizures, which leads us to a deeper understanding of epileptogenesis and points to a promising direction for epilepsy treatment.

中文翻译：

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通过破坏和扰乱癫痫记忆印迹来终止惊厥发作

癫痫发生是由突触强度的改变引起的，与记忆形成在机制和表型上有相似之处。然而，支持癫痫记忆存在的直接证据仍然很少。利用条件性癫痫发作记忆（CSM）范式，我们发现CSM能够使环境线索重复触发癫痫发作，并且激活线索响应印迹细胞可以人为地生成CSM。此外，线索暴露启动了由雷帕霉素-脑源性神经营养因子信号传导的哺乳动物靶标驱动的类似的记忆重建过程。在有限的时间窗口内对雷帕霉素途径的哺乳动物靶标进行药理学靶向可减少动物的癫痫发作和难治性癫痫发作患者的发作间期癫痫样放电。我们的研究结果揭示了癫痫发作记忆印迹与癫痫发作之间的因果关系，这使我们对癫痫发生有了更深入的了解，并为癫痫治疗指明了一个有希望的方向。