Zhao Peilin, Ding Xiaomi, Li Lini, Jiang Guohui
Institute of Neurological Diseases, Affiliated Hospital of Clinical School of Medicine, North Sichuan Medical College, Nanchong, Sichuan, 637000, China.
Nanomedicine Innovation Research and Development Transformation Institute, Affiliated Hospital of Clinical School of Medicine, North Sichuan Medical College, Nanchong, Sichuan, 637000, China.
Acta Epileptol. 2024 Jun 1;6(1):18. doi: 10.1186/s42494-024-00159-2.
Epilepsy is a prevalent neurological disorder, yet its underlying mechanisms remain incompletely understood. Accumulated studies have indicated that epilepsy is characterized by abnormal neural circuits. Understanding the circuit mechanisms is crucial for comprehending the pathogenesis of epilepsy. With advances in tracing and modulating tools for neural circuits, some epileptic circuits have been uncovered. This comprehensive review focuses on the circuit mechanisms underlying epilepsy in various neuronal subtypes, elucidating their distinct roles. Epileptic seizures are primarily characterized by the hyperactivity of glutamatergic neurons and inhibition of GABAergic neurons. However, specific activated GABAergic neurons and suppressed glutamatergic neurons exacerbate epilepsy through preferentially regulating the activity of GABAergic neurons within epileptic circuits. Distinct subtypes of GABAergic neurons contribute differently to epileptic activities, potentially due to their diverse connection patterns. Moreover, identical GABAergic neurons may assume distinct roles in different stages of epilepsy. Both GABAergic neurons and glutamatergic neurons with long-range projecting fibers innervate multiple nuclei; nevertheless, not all of these circuits contribute to epileptic activities. Epileptic circuits originating from the same nuclei may display diverse contributions to epileptic activities, and certain glutamatergic circuits from the same nuclei may even exert opposing effects on epilepsy. Neuromodulatory neurons, including cholinergic, serotonergic, dopaminergic, and noradrenergic neurons, are also implicated in epilepsy, although the underlying circuit mechanisms remain poorly understood. These studies suggest that epileptic nuclei establish intricate connections through cell-type-specific circuits and play pivotal roles in epilepsy. However, there are still limitations in knowledge and methods, and further understanding of epileptic circuits is crucial, particularly in the context of refractory epilepsy.
癫痫是一种常见的神经系统疾病，但其潜在机制仍未完全明确。大量研究表明，癫痫的特征是神经回路异常。了解回路机制对于理解癫痫的发病机制至关重要。随着神经回路追踪和调节工具的进步，一些癫痫回路已被发现。这篇综述聚焦于不同神经元亚型中癫痫的回路机制，阐明它们的不同作用。癫痫发作主要表现为谷氨酸能神经元的过度活跃和γ-氨基丁酸能神经元的抑制。然而，特定激活的γ-氨基丁酸能神经元和受抑制的谷氨酸能神经元通过优先调节癫痫回路中γ-氨基丁酸能神经元的活性而加剧癫痫。不同亚型的γ-氨基丁酸能神经元对癫痫活动的贡献不同，这可能是由于它们不同的连接模式。此外，相同的γ-氨基丁酸能神经元在癫痫的不同阶段可能发挥不同的作用。具有长程投射纤维的γ-氨基丁酸能神经元和谷氨酸能神经元都支配多个核团；然而，并非所有这些回路都参与癫痫活动。源自同一核团的癫痫回路对癫痫活动可能有不同的贡献，并且来自同一核团的某些谷氨酸能回路甚至可能对癫痫产生相反的作用。神经调节神经元，包括胆碱能、5-羟色胺能、多巴胺能和去甲肾上腺素能神经元，也与癫痫有关，尽管其潜在的回路机制仍知之甚少。这些研究表明，癫痫核团通过细胞类型特异性回路建立复杂的连接，并在癫痫中起关键作用。然而，在知识和方法上仍存在局限性，进一步了解癫痫回路至关重要，特别是在难治性癫痫的背景下。
