Ren Hui, Shi Ye-Jun, Lu Qin-Chi, Liang Pei-Ji, Zhang Pu-Ming
School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Theor Biol Med Model. 2014 Mar 24;11:14. doi: 10.1186/1742-4682-11-14.
Temporal lobe epilepsy (TLE) is the commonest type of epilepsy in adults, and the hippocampus is indicated to have a close relationship with TLE. Recent researches also indicate that the entorhinal cortex (EC) is involved in epilepsy. To explore the essential role that the EC may play in epilepsy, a computational model of the hippocampal CA3 region was built, which consisted of pyramidal cells and two types of interneurons. By changing the input signals from the EC, the effects of EC on epileptiform activities of the hippocampus were investigated. Additionally, recent studies have found that the antiepileptic drug valproate (VPA) can block ictal discharges but cannot block interictal discharges in vitro, and the mechanism under this phenomenon is still confusing. In our model, the effects of VPA on epileptiform activities were simulated and some mechanisms were explored.
Interictal discharges were induced in the model without the input signals from the EC, whereas the model with the EC input produced ictal discharges when the EC input contained ictal discharges. The GABA-ergic connection strength was enhanced and the NMDA-ergic connection strength was reduced to simulate the effects of VPA, and the simulation results showed that the disappearance of ictal discharges in the model mainly due to the disappearance of ictal discharges in the input signals from the EC.
Simulation results showed that ictal discharges in the EC were necessary for the hippocampus to generate ictal discharges, and VPA might block the ictal discharges in the EC, which led to the disappearance of ictal discharges in the hippocampus.
颞叶癫痫(TLE)是成人中最常见的癫痫类型,海马体被认为与TLE关系密切。近期研究还表明内嗅皮质(EC)参与癫痫发作。为探究EC在癫痫中可能发挥的关键作用,构建了一个海马体CA3区的计算模型,该模型由锥体细胞和两种中间神经元组成。通过改变来自EC的输入信号,研究了EC对海马体癫痫样活动的影响。此外,近期研究发现抗癫痫药物丙戊酸(VPA)在体外可阻断发作期放电,但不能阻断发作间期放电,这种现象背后的机制仍不清楚。在我们的模型中,模拟了VPA对癫痫样活动的影响并探究了一些机制。
在没有来自EC的输入信号时,模型中诱发了发作间期放电,而当EC输入包含发作期放电时,具有EC输入的模型产生了发作期放电。增强GABA能连接强度并降低NMDA能连接强度以模拟VPA的作用,模拟结果表明模型中发作期放电的消失主要是由于来自EC的输入信号中发作期放电的消失。
模拟结果表明,EC中的发作期放电是海马体产生发作期放电所必需的,VPA可能阻断了EC中的发作期放电,从而导致海马体中发作期放电的消失。