Temporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. The reorganization of the dentate gyrus (DG) in TLE may create pathological conduction pathways for synchronous discharges in the temporal lobe, though critical microcircuit-level detail is missing from this pathophysiological intuition. In particular, the relative contribution of adult-born (abGC) and mature (mGC) granule cells to epileptiform network events remains unknown. We assess dynamics of abGCs and mGCs during interictal epileptiform discharges (IEDs) in mice with TLE as well as sharp-wave ripples (SPW-Rs) in healthy mice, and find that abGCs and mGCs are desynchronized and differentially recruited by IEDs compared to SPW-Rs. We introduce a neural topic model to explain these observations, and find that epileptic DG networks organize into disjoint, cell-type specific pathological ensembles in which abGCs play an outsized role. Our results characterize identified GC subpopulation dynamics in TLE, and reveal a specific contribution of abGCs to IEDs.

颞叶癫痫 (TLE) 的特点是由同步神经元活动驱动的反复发作。 TLE 中齿状回 (DG) 的重组可能会为颞叶中的同步放电创建病理传导通路，尽管这种病理生理学直觉中缺少关键的微电路级细节。特别是，成人出生（abGC）和成熟（mGC）颗粒细胞对癫痫样网络事件的相对贡献仍然未知。我们评估了 TLE 小鼠发作间期癫痫样放电 (IED) 期间的 abGCs 和 mGCs 以及健康小鼠的尖波波纹 (SPW-Rs) 的动态，发现与 SPW 相比，IEDs 的 abGCs 和 mGCs 不同步且有差异性招募-卢比。我们引入神经主题模型来解释这些观察结果，并发现癫痫 DG 网络组织成不相交的、细胞类型特定的病理学整体，其中 abGC 发挥着巨大的作用。我们的结果描述了 TLE 中已识别的 GC 亚群动态，并揭示了 abGC 对 IED 的具体贡献。