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

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 th...

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Main Authors: Mingming Chen, Daqing Guo, Min Li, Tao Ma, Shengdun Wu, Jingling Ma, Yan Cui, Yang Xia, Peng Xu, Dezhong Yao
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-10-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1004539
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spelling doaj-58b5a719cba348f4ae448c6ad387e4172021-04-21T14:59:24ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582015-10-011110e100453910.1371/journal.pcbi.1004539Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures.Mingming ChenDaqing GuoMin LiTao MaShengdun WuJingling MaYan CuiYang XiaPeng XuDezhong YaoThe 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.https://doi.org/10.1371/journal.pcbi.1004539
collection DOAJ
language English
format Article
sources DOAJ
author Mingming Chen
Daqing Guo
Min Li
Tao Ma
Shengdun Wu
Jingling Ma
Yan Cui
Yang Xia
Peng Xu
Dezhong Yao
spellingShingle Mingming Chen
Daqing Guo
Min Li
Tao Ma
Shengdun Wu
Jingling Ma
Yan Cui
Yang Xia
Peng Xu
Dezhong Yao
Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures.
PLoS Computational Biology
author_facet Mingming Chen
Daqing Guo
Min Li
Tao Ma
Shengdun Wu
Jingling Ma
Yan Cui
Yang Xia
Peng Xu
Dezhong Yao
author_sort Mingming Chen
title Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures.
title_short Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures.
title_full Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures.
title_fullStr Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures.
title_full_unstemmed Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures.
title_sort critical roles of the direct gabaergic pallido-cortical pathway in controlling absence seizures.
publisher Public Library of Science (PLoS)
series PLoS Computational Biology
issn 1553-734X
1553-7358
publishDate 2015-10-01
description 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.
url https://doi.org/10.1371/journal.pcbi.1004539
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