Henan Key Laboratory of Brain Science and Brain-Computer Interface Technology, School of Electrical Engineering, Zhengzhou University, Zhengzhou 450001, People's Republic of China.
Henan Key Laboratory of Brain Science and Brain-Computer Interface Technology, School of Electrical Engineering, Zhengzhou University, Zhengzhou 450001, People's Republic of China.
Neural Netw. 2021 Mar;135:78-90. doi: 10.1016/j.neunet.2020.12.006. Epub 2020 Dec 14.
Absence epilepsy, characterized by transient loss of awareness and bilaterally synchronous 2-4 Hz spike and wave discharges (SWDs) on electroencephalography (EEG) during absence seizures, is generally believed to arise from abnormal interactions between the cerebral cortex (Ctx) and thalamus. Recent animal electrophysiological studies suggested that changing the neural activation level of the external globus pallidus (GPe) neurons can remarkably modify firing rates of the thalamic reticular nucleus (TRN) neurons through the GABAergic GPe-TRN pathway. However, the existing experimental evidence does not provide a clear answer as to whether the GPe-TRN pathway contributes to regulating absence seizures. Here, using a biophysically based mean-field model of the GPe-corticothalamic (GCT) network, we found that both directly decreasing the strength of the GPe-TRN pathway and inactivating GPe neurons can effectively suppress absence seizures. Also, the pallido-cortical pathway and the recurrent connection of GPe neurons facilitate the regulation of absence seizures through the GPe-TRN pathway. Specifically, in the controllable situation, enhancing the coupling strength of either of the two pathways can successfully terminate absence seizures. Moreover, the competition between the GPe-TRN and pallido-cortical pathways may lead to the GPe bidirectionally controlling absence seizures, and this bidirectional control manner can be significantly modulated by the Ctx-TRN pathway. Importantly, when the strength of the Ctx-TRN pathway is relatively strong, the bidirectional control of absence seizures by changing GPe neural activities can be observed at both weak and strong strengths of the pallido-cortical pathway.These findings suggest that the GPe-TRN pathway may have crucial functional roles in regulating absence seizures, which may provide a testable hypothesis for further experimental studies and new perspectives on the treatment of absence epilepsy.
失神发作，以脑电图（EEG）记录到发作期间短暂意识丧失及双侧同步 2-4Hz 棘慢波放电（SWD）为特征，一般认为是由大脑皮层（Ctx）与丘脑之间的异常相互作用引起的。最近的动物电生理研究表明，改变苍白球外部（GPe）神经元的神经激活水平，可以通过 GABA 能的 GPe-TRN 通路显著改变丘脑网状核（TRN）神经元的放电率。然而，现有的实验证据并不能明确回答 GPe-TRN 通路是否有助于调节失神发作。在这里，我们使用基于 GPe-皮质丘脑（GCT）网络的生物物理均值场模型，发现直接降低 GPe-TRN 通路的强度和使 GPe 神经元失活，都能有效抑制失神发作。此外，苍白球皮质通路和 GPe 神经元的回传连接通过 GPe-TRN 通路促进了失神发作的调节。具体来说，在可控的情况下，增强这两条通路中的任何一条的耦合强度都可以成功终止失神发作。此外，GPe-TRN 通路与苍白球皮质通路之间的竞争可能导致 GPe 双向控制失神发作，而这种双向控制方式可以被 Ctx-TRN 通路显著调节。重要的是，当 Ctx-TRN 通路的强度相对较强时，通过改变 GPe 神经活动来双向控制失神发作，可以在苍白球皮质通路的弱和强两种强度下观察到。这些发现表明，GPe-TRN 通路可能在调节失神发作中具有关键的功能作用，这可能为进一步的实验研究和失神性癫痫的治疗提供一个可检验的假说。
