Dynamic Transitions in Neuronal Network Firing Sustained by Abnormal Astrocyte Feedback.

Yangyang Yu,Zhixuan Yuan,Jiajia Li,Ying Wu,Yongchen Fan,Rubin Wang

doi:10.1155/2020/8864246

Abstract

Astrocytes play a crucial role in neuronal firing activity. Their abnormal state may lead to the pathological transition of neuronal firing patterns and even induce seizures. However, there is still little evidence explaining how the astrocyte network modulates seizures caused by structural abnormalities, such as gliosis. To explore the role of gliosis of the astrocyte network in epileptic seizures, we first established a direct astrocyte feedback neuronal network model on the basis of the hippocampal CA3 neuron-astrocyte model to simulate the condition of gliosis when astrocyte processes swell and the feedback to neurons increases in an abnormal state. We analyzed the firing pattern transitions of the neuronal network when astrocyte feedback starts to change via increases in both astrocyte feedback intensity and the connection probability of astrocytes to neurons in the network. The results show that as the connection probability and astrocyte feedback intensity increase, neuronal firing transforms from a nonepileptic synchronous firing state to an asynchronous firing state, and when astrocyte feedback starts to become abnormal, seizure-like firing becomes more severe and synchronized; meanwhile, the synchronization area continues to expand and eventually transforms into long-term seizure-like synchronous firing. Therefore, our results prove that astrocyte feedback can regulate the firing of the neuronal network, and when the astrocyte network develops gliosis, there will be an increase in the induction rate of epileptic seizures.

Highlights

Epilepsy is one of the most common neurological diseases, affecting nearly 70 million people worldwide, and it is characterized by the aberrant synchronous firing of neurons [1,2,3]
Because experiments have shown that the increased excitability of interneurons is beneficial in enhancing the inhibition of the nervous system and suppressing seizures [55,56,57], we studied the impact of changes in the connection probability of P1 with P2 = 0.8, P2 with P1 = 0.8, and the astrocyte feedback intensity γ2 from astrocytes to interneurons on pyramidal neuronal population synchronous firing with gse = 2
We used a new model to study the effects of astrocyte feedback on neuronal population firing and the generation and development of epilepsy in gliosis

Summary

Introduction

Epilepsy is one of the most common neurological diseases, affecting nearly 70 million people worldwide, and it is characterized by the aberrant synchronous firing of neurons [1,2,3]. Astrocytes can respond to the stimulation of neuronal activity and release glial transmitters to regulate neuronal firing, and the concept of “tripartite synapse” is proposed to describe the bidirectional communication between astrocytes and neurons [18]. Many physiological experiments have shown that when astrocytes have abnormal functioning, this will lead to seizure-like events such as the aberrant synchronous firing of neurons [10, 17, 19, 20], and through mathematical modeling methods, many researchers have studied the possibility of dysfunctional astrocytes participating in neuronal epilepsy [21,22,23,24,25,26,27,28]. Amiri et al studied the effect of Ca2+ oscillations in astrocyte clusters on the firing of neuronal populations by constructing a “tripartite synapse” network

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Results

Conclusion