Channel block of the astrocyte network connections accounting for the dynamical transition of epileptic seizures

Jiajia Li,Chenglong Cao,Jian Song,Shengjun Xu,Mengmeng Du,Ning Tan,Ying Wu

doi:10.1007/s11071-021-06737-0

Abstract

Epilepsy has been found to be modulated by the astrocyte systems in experiments, and tremendous modeling studies have unveiled the roles of astrocyte cellular functions such as the calcium and potassium channels in the epileptic seizures. However, little attention has been paid to the structure changes of astrocytes in the epileptic seizures in the scale of networks. This paper first constructs a neuron–astrocyte network model to explain the experimental observation that astrocytes mainly induce epilepsy by blocking the channels of the astrocyte gap junction in the network scale. Such model is used to discuss potential seizure induction process in the network by changing the connection intensity of the astrocyte gap junction. The simulation results show that a decrease of the gap junction intensity changes the firing pattern of the population of neurons from slow periodical firing to high-frequency epileptic seizures, featuring epileptic patterns of depolarization blocks. This further verifies that epileptic seizures are experimentally induced via the channel block of the astrocyte gap junctions. Because of the heterogeneous structure of the real neuron–astrocyte network, the effect of changing astrocyte network structures on the seizure activities is then studied in two typical network structures: the regular neighboring connection and the random connection. The results show that an increase of the number of regular connections of the regular neighboring astrocyte network could inhibit the induction and spread of the epileptic seizures. The epileptic inhibition can be achieved similarly by increasing the connection probability of the random astrocyte network. These findings further provide evidence for the experimental phenomena of the protective response of gliosis to epilepsy with increasing gap junctions. Above all, the simulation results suggest a potential pathway of epilepsy treatment by targeting the astrocyte gap junctions.

Highlights

Mengmeng Du Shaanxi University of Science and Technology Xi\'an Campus: Shaanxi University of Science and Technology Shengjun Xu
Wei et al have unfold the intrinsic mechanisms of astrocytes modulating the blood oxygen that is related to brain epilepsy or cerebral stroke spread[25], Our team have modeled the gliotransmittor dynamic model to have proved a specific epileptic pathway dominated by the degradation abnormality of the astrocyte-released glutamate[26]
For unfolding underlying mechanisms of the blocked gap- junction channels in epilepsy, we have studied the decreases of the astrocyte gap junction intensity gA-A on epileptic seizures

Summary

Introduction

Epilepsy has long been accepted as a refractory brain disorder, characterized by recurrent seizures. Utilizing the concept of “tripartite synapses”, many researchers have utilized modeling tools to investigate the dynamic transitions of seizures modulated by astrocytes and their released chemicals in single cells as well as networks of astrocytes and neurons [23,24,25,26,27,28,29]. To unravel the effects of IP3-flux gap junctions of the astrocyte network and its topology on the neuronal network firing dynamics, this paper constructs a neuron-astrocyte network model. This model includes pyramidal cells with electrical connections and astrocytes coupled with gap junctions. Where Vca represents the reversal potential of the calcium channel at the dendrite terminal

Synchronization factor

Glutamate released by the astrocyte network sustains seizure induction

Conclusions and Discussions