Department of Neurosurgery, Stanford University, Stanford, CA, USA.
Department of Pharmacology and the Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA.
Nat Med. 2024 May;30(5):1292-1299. doi: 10.1038/s41591-024-02924-9. Epub 2024 Apr 17.
Targeted tissue ablation involving the anterior hippocampus is the standard of care for patients with drug-resistant mesial temporal lobe epilepsy. However, a substantial proportion continues to suffer from seizures even after surgery. We identified the fasciola cinereum (FC) neurons of the posterior hippocampal tail as an important seizure node in both mice and humans with epilepsy. Genetically defined FC neurons were highly active during spontaneous seizures in epileptic mice, and closed-loop optogenetic inhibition of these neurons potently reduced seizure duration. Furthermore, we specifically targeted and found the prominent involvement of FC during seizures in a cohort of six patients with epilepsy. In particular, targeted lesioning of the FC in a patient reduced the seizure burden present after ablation of anterior mesial temporal structures. Thus, the FC may be a promising interventional target in epilepsy.
针对耐药性内侧颞叶癫痫患者,靶向前海马组织消融术是标准的治疗方法。然而,手术后仍有相当一部分患者继续遭受癫痫发作的困扰。我们发现,在癫痫小鼠和人类中,后海马尾部的灰结节 Fasciola cinereum(FC)神经元是一个重要的致痫节点。在癫痫小鼠的自发性癫痫发作期间,遗传定义的 FC 神经元高度活跃,而对这些神经元进行闭环光遗传抑制则可显著减少癫痫发作持续时间。此外,我们在一组 6 名癫痫患者中发现并证实了 FC 在癫痫发作中的显著作用。特别是,在一名患者中对 FC 进行靶向损伤,可减少前内侧颞叶结构消融术后的癫痫发作负担。因此,FC 可能是癫痫的一个有前途的干预靶点。