Research On The Role Of The Entorhinal Cortex In Epileptiform Activities Of The Hippocampus Based On The Computational Model

Temporal lobe epilepsy is one of the common forms of adult epilepsy, and mostpatients with temporal lobe epilepsy are considered to have drug-resistant epilepsy.Entorhinal cortex (EC) and hippocampus are important parts of the limbic system, andthey both play essential roles in the generation of temporal lobe epilepsy. Accordingto experimental studies, after the application of Mg2+-free artificial cerebrospinal fluid(ACSF), interictal-like discharges occurred in hippocampal slices, and interictal-likeand ictal-like discharges occurred in combined EC-hippocampal slices. Thus, wesuggested that EC might have a close relationship with the generation of ictal-likedischarges of the hippocampus. Valproate (VPA) is one of the common antiepilepticdrugs used today. According to experimental studies, VPA couldn’t blockinterictal-like discharges but could block ictal-like discharges of the combinedEC-hippocampal slices. The mechanism under this phenomenon is still unknown. Inour model, the effects of VPA on epileptiform activities were simulated and somemechanisms of this phenomenon were explored.The main contents of this article include three parts.(1) A computational modelof the hippocampal CA3region was built. Two pyramidal cells, one basket cell andone oriens-lacunosum molecular cell were chosen to build the model, and theirconnectivities and the distribution of receptors were based on anatomical studies.(2)In the model without input from EC, interictal-like discharges of the hippocampalslices induced by Mg2+-free ACSF were simulated by changing the Mg2+concentration in the model. In the model with input from EC, interictal-like andictal-like discharges of the combined EC-hippocampal slices induced by Mg2+-freeACSF were simulated.(3) GABA-ergic inhibitory connection strength was enhancedand NMDA-ergic excitatory connection strength was reduced to simulate the effectsof VPA on epileptiform activities. According to these researches, we found that the hippocampal CA3region couldgenerate interictal-like discharges by changing the Mg2+concentration to0mM, andthe model could also generate ictal-like discharges when input signals from EC wereadded, which contained ictal-like discharges, into the model. These results suggestedthat EC could induce the hippocampus to generate ictal-like discharges in combinedEC-hippocampal slices. In the model without input from EC, when the GABA-ergicinhibitory connection strength was enhanced and NMDA-ergic excitatory connectionstrength was reduced, the frequency of interictal-like discharges decreased. In themodel with input from EC, when input signals from EC only contained interictal-likedischarges, the model produced interictal-like discharges. Enhancing GABA-ergicinhibitory connection strength and reducing NMDA-ergic excitatory connectionstrength of the model, interictal-like discharges still existed. However, when inputsignals from EC consisted of interictal-like and ictal-like discharges, the modelproduced interictal-like and ictal-like discharges. Enhancing GABA-ergic inhibitoryconnection strength and reducing NMDA-ergic excitatory connection strengthcouldn’t block the ictal-like discharges. As the ictal-like discharges of the modeldisappeared when the input signals from EC didn’t contain ictal-like discharges, wesupposed that the disappearance of ictal-like discharges in the hippocampus ofcombined EC-hippocampal slices might due to the disappearance of ictal-likedischarges of the EC. In this way, we deduced that VPA might block the ictal-likedischarges of the EC in combined EC-hippocampal slices, which led to thedisappearance of ictal-like discharges of the hippocampus.In this paper, we built a computational model of the hippocampal CA3region todo some researches about the effects of EC on epileptiform activities of thehippocampus. By changing the input from EC, some experimental phenomena weresimulated and mechanisms under these phenomena were explored. The model webuilt here is very useful, and it can also be used to do researches about otherepileptiform activities in future studies.