Department of Neuroscience, Columbia University, New York, NY, USA.
Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.
Nat Commun. 2020 Dec 1;11(1):6138. doi: 10.1038/s41467-020-19969-2.
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）的特征是反复的癫痫发作，由同步的神经元活动驱动。TLE 中海马齿状回（DG）的重组可能为颞叶中的同步放电创建病理性传导途径，但这种病理生理学直觉缺乏关键的微电路级细节。特别是，成年新生（abGC）和成熟（mGC）颗粒细胞对癫痫网络事件的相对贡献仍不清楚。我们评估了 TLE 小鼠的癫痫样放电（IEDs）期间 abGCs 和 mGCs 的动力学以及健康小鼠的尖波涟漪（SPW-Rs），发现与 SPW-Rs 相比，abGCs 和 mGCs 在 IEDs 期间去同步化并且被不同程度地募集。我们引入了一个神经主题模型来解释这些观察结果，并发现癫痫性 DG 网络组织成不相交的、细胞类型特异性的病理性集合，其中 abGCs 起着重要作用。我们的结果描述了 TLE 中已识别的 GC 亚群动力学，并揭示了 abGCs 对 IEDs 的特定贡献。
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