Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures.

Mingming Chen,Yan Cui,Jingling Ma,Daqing Guo,Tao Ma,Min Li,Shengdun Wu,Yang Xia,Dezhong Yao,Peng Xu,Gustavo Deco

doi:10.1371/journal.pcbi.1004539

Abstract

The basal ganglia (BG), serving as an intermediate bridge between the cerebral cortex and thalamus, are believed to play crucial roles in controlling absence seizure activities generated by the pathological corticothalamic system. Inspired by recent experiments, here we systematically investigate the contribution of a novel identified GABAergic pallido-cortical pathway, projecting from the globus pallidus externa (GPe) in the BG to the cerebral cortex, to the control of absence seizures. By computational modelling, we find that both increasing the activation of GPe neurons and enhancing the coupling strength of the inhibitory pallido-cortical pathway can suppress the bilaterally synchronous 2–4 Hz spike and wave discharges (SWDs) during absence seizures. Appropriate tuning of several GPe-related pathways may also trigger the SWD suppression, through modulating the activation level of GPe neurons. Furthermore, we show that the previously discovered bidirectional control of absence seizures due to the competition between other two BG output pathways also exists in our established model. Importantly, such bidirectional control is shaped by the coupling strength of this direct GABAergic pallido-cortical pathway. Our work suggests that the novel identified pallido-cortical pathway has a functional role in controlling absence seizures and the presented results might provide testable hypotheses for future experimental studies.

Highlights

Epilepsy is a paroxysmal behavior caused by abnormal, excessive or hypersynchronous discharges of neurons in the brain [1, 2]
As intriguing deep nuclei of brain, the basal ganglia are reported to play crucial roles in controlling absence seizures through multiple nigro-thalamic pathways. Beside these nigro-thalamic pathways, recent experiments have identified a new direct GABAergic pallido-cortical pathway projecting from the globus pallidus externa (GPe) to the cerebral cortex
Similar to previous modelling studies [21, 28,29,30], the globus pallidus internal (GPi) segment is regarded as a single structure with substantia nigra pars reticulata (SNr) in our model, because they have the similar properties in both neural function and anatomical connectivity [28, 29]

Summary

Introduction

Epilepsy is a paroxysmal behavior caused by abnormal, excessive or hypersynchronous discharges of neurons in the brain [1, 2]. Absence epilepsy (AE) is a subtype of idiopathic generalized epilepsy and mainly occurs in the childhood years [3, 4]. Experimental studies showed that a typical attack of absence seizures commonly causes a sudden onset and offset of spikewave activities, accompanying with temporary loss of consciousness. A large number of studies have been performed to investigate the generation mechanisms of typical SWDs during absence seizures [6,7,8]. There is accumulating evidence that such type of SWDs is highly associated with the abnormal interactions between cerebral cortex and thalamus, and appropriately regulating the pathological corticothalamic system may control absence seizures [9,10,11,12,13,14]

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Discussion

Conclusion