Institute of Neurobiology, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro, Querétaro, Mexico.
Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Sci Rep. 2023 Jul 30;13(1):12335. doi: 10.1038/s41598-023-38717-2.
Focal cortical dysplasias (FCDs) are malformations of cortical development that often result in medically refractory epilepsy, with a greater incidence in the pediatric population. The relationship between the disturbed cortical morphology and epileptogenic activity of FCDs remains unclear. We used the BCNU (carmustine 1-3-bis-chloroethyl-nitrosourea) animal model of cortical dysplasia to evaluate neuronal and laminar alterations and how these result in altered activity of intracortical networks in early life. We corroborated the previously reported morphological anomalies characteristic of the BCNU model, comprising slightly larger and rounder neurons and abnormal cortical lamination. Next, the neuronal activity of live cortical slices was evaluated through large field-of-view calcium imaging as well as the neuronal response to a stimulus that leads to cortical hyperexcitability (pilocarpine). Examination of the joint activity of neuronal calcium time series allowed us to identify intracortical communication patterns and their response to pilocarpine. The baseline power density distribution of neurons in the cortex of BCNU-treated animals was different from that of control animals, with the former showing no modulation after stimulus. Moreover, the intracortical communication pattern differed between the two groups, with cortexes from BCNU-treated animals displaying decreased inter-layer connectivity as compared to control animals. Our results indicate that the altered anatomical organization of the cortex of BCNU-treated rats translates into altered functional networks that respond abnormally to a hyperexcitable stimulus and highlight the role of network dysfunction in the pathophysiology of cortical dysplasia.
局灶性皮质发育不良（FCDs）是皮质发育畸形，常导致药物难治性癫痫，儿科人群发病率较高。皮质形态异常与 FCD 致痫活性之间的关系尚不清楚。我们使用 BCNU（卡莫司汀 1-3-双氯乙基-亚硝脲）皮质发育不良动物模型，评估神经元和层状改变，以及这些改变如何导致皮质发育不良动物早期皮质内网络活动改变。我们证实了先前报道的 BCNU 模型的形态异常，包括稍大且更圆的神经元和异常的皮质分层。接下来，通过大视野钙成像评估活皮质切片的神经元活动，以及神经元对导致皮质过度兴奋的刺激（毛果芸香碱）的反应。检查神经元钙时间序列的联合活动，使我们能够识别皮质内通讯模式及其对毛果芸香碱的反应。BCNU 处理动物皮质中神经元的基线功率密度分布与对照动物不同，前者在刺激后没有调制。此外，两组之间的皮质内通讯模式也不同，与对照动物相比，BCNU 处理动物的皮质表现出层间连接减少。我们的结果表明，BCNU 处理大鼠皮质的解剖组织改变转化为功能网络的改变，对过度兴奋的刺激反应异常，并强调了网络功能障碍在皮质发育不良病理生理学中的作用。
