Multi-modal characterization and simulation of human epileptic circuitry.
Multi-modal characterization and simulation of human epileptic circuitry.
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DOI：
10.1016/j.celrep.2022.111873
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发表时间：
2022-12-27
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
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颞叶癫痫是第四大常见的神经系统疾病，约 40% 的患者对药物治疗没有反应。细胞损失增加与疾病严重程度和病理表型（例如癫痫发作倾向增加）有关。虽然海马体是治疗干预的目标，但该疾病在细胞水平上的影响仍不清楚。在这里，我们通过从癫痫患者身上切除的活海马组织进行测量，发现海马颗粒细胞随着疾病进展而变化。我们发现颗粒细胞增加了兴奋性并缩短了反应潜伏期，同时也增加了细胞体积和脊柱密度。单核 RNA 测序结合模拟将变化归因于三种电导：BK、Cav2.2 和 Kir2.1。在网络模型中，我们表明，这些与疾病进展相关的变化使回路进入更兴奋的状态，而逆转它们会产生不太兴奋的“类似早期疾病”的状态。颞叶癫痫给人类带来的细胞变化仍然未知。布钦等人。从人类海马手术组织生成多模态数据集，以绘制与疾病进展相关的细胞变化。他们发现三种离子电导可以解释不同模式的变化。
Temporal lobe epilepsy is the fourth most common neurological disorder, with about 40% of patients not responding to pharmacological treatment. Increased cellular loss is linked to disease severity and pathological phenotypes such as heightened seizure propensity. While the hippocampus is the target of therapeutic interventions, the impact of the disease at the cellular level remains unclear. Here, we show that hippocampal granule cells change with disease progression as measured in living, resected hippocampal tissue excised from patients with epilepsy. We show that granule cells increase excitability and shorten response latency while also enlarging in cellular volume and spine density. Single-nucleus RNA sequencing combined with simulations ascribes the changes to three conductances: BK, Cav2.2, and Kir2.1. In a network model, we show that these changes related to disease progression bring the circuit into a more excitable state, while reversing them produces a less excitable, “early-disease-like” state. The cellular changes brought about by temporal lobe epilepsy in humans remain unknown. Buchin et al. generate a multimodal dataset from human hippocampal surgical tissue to map cellular changes linked to disease progression. They find three ion conductances that explain changes across modalities.
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影响因子：
9.9
作者：
Kälviäinen, R;Salmenperä, T;Pitkänen, A
通讯作者：
Pitkänen, A
影响因子：
16.2
作者：
Kalmbach BE;Buchin A;Long B;Close J;Nandi A;Miller JA;Bakken TE;Hodge RD;Chong P;de Frates R;Dai K;Maltzer Z;Nicovich PR;Keene CD;Silbergeld DL;Gwinn RP;Cobbs C;Ko AL;Ojemann JG;Koch C;Anastassiou CA;Lein ES;Ting JT
通讯作者：
Ting JT
影响因子：
5.6
作者：
Heng K;Haney MM;Buckmaster PS
通讯作者：
Buckmaster PS
影响因子：
30.8
作者：
Du, W;Bautista, JF;Wang, QK
通讯作者：
Wang, QK
影响因子：
64.8
作者：
Hodge, Rebecca D.;Bakken, Trygve E.;Lein, Ed S.
通讯作者：
Lein, Ed S.