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

Chen, Mingming; Guo, Daqing; Li, Min; Ma, Tao; Wu, Shengdun; Ma, Jingling; Cui, Yan; Yang, Xiaobo; Xu, Peng; Yao, Dezhong

doi:10.1371/journal.pcbi.1004539

Cited by 67 publications

(68 citation statements)

References 62 publications

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“…The temporal resolution of numerical integration is fixed at 1 ms. All simulations are performed up to 20 s and the data of the stable state after a time interval of 5 s are used for analysis. Both the bifurcation and frequency analysis558586 are utilized to characterize the critical state transitions and neural oscillations generated by our model. Firstly, to explore the transitions between various dynamical states, the bifurcation analysis is performed for several critical cortical parameters.…”

Section: Methodsmentioning

confidence: 99%

Stimulus-induced Epileptic Spike-Wave Discharges in Thalamocortical Model with Disinhibition

Fan

Liu

Wang

2016

Sci Rep

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Epileptic absence seizure characterized by the typical 2–4 Hz spike-wave discharges (SWD) are known to arise due to the physiologically abnormal interactions within the thalamocortical network. By introducing a second inhibitory neuronal population in the cortical system, here we propose a modified thalamocortical field model to mathematically describe the occurrences and transitions of SWD under the mutual functions between cortex and thalamus, as well as the disinhibitory modulations of SWD mediated by the two different inhibitory interneuronal populations. We first show that stimulation can induce the recurrent seizures of SWD in the modified model. Also, we demonstrate the existence of various types of firing states including the SWD. Moreover, we can identify the bistable parametric regions where the SWD can be both induced and terminated by stimulation perturbations applied in the background resting state. Interestingly, in the absence of stimulation disinhibitory functions between the two different interneuronal populations can also both initiate and abate the SWD, which suggests that the mechanism of disinhibition is comparable to the effect of stimulation in initiating and terminating the epileptic SWD. Hopefully, the obtained results can provide theoretical evidences in exploring dynamical mechanism of epileptic seizures.

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Section: Methodsmentioning

confidence: 99%

Stimulus-induced Epileptic Spike-Wave Discharges in Thalamocortical Model with Disinhibition

Fan

Liu

Wang

2016

Sci Rep

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“…Unless otherwise noted, we use the follow parameter values for simulations [8,9,10,11,12,31,32,33,34]…”

Section: Appendixmentioning

confidence: 99%

“…And then, in 2015, Hu and Wang applied one type of deep brain stimulation(DBS) voltage on the SNr and the excitatory pyramidal neurons of cortex in BGCT, and they found that seizures can be well controlled by tuning some parameters of the stimulation current into appropriate ranges [11]. Recently, Chen et al found that the direct γ-aminobutyric acid (GABAergic) pallido-cortical pathway also plays a key role in controlling absence epilepsy [12]. They are good tools for predicting seizures in theory [3,7,10,12] and some even may guide strategies for therapy epilepsy by pharmacological, surgical and electrical stimulation techniques [5,9,11].…”

Section: Introductionmentioning

confidence: 99%

Controlling absence seizures by tuning activation level of the thalamus and striatum

Chen

Chi

et al. 2017

Chaos, Solitons & Fractals

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In this paper, we use a basal ganglia-corticothalamic model(BGCT) to study control effect of the absence epilepsy seizure. It is shown that the seizure state can be well controlled by tuning activation level of the thalamic reticular nucleus (TRN), specific relay nuclei (SRN), striatal D1 neurons and striatal D2 neurons. And then, one type of deep brain stimulation voltage employed on SRN, we find that seizure activities can also be controlled by tuning the period (P) and the duration of effective current (D) in a period into some appropriate ranges. So, we infer that the thalamic and striatal tissue may become effective target regions in clinical treatment of epilepsy in the future.

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“…Then, we describe the simulation methods, the 68 analytical calculations of steady states and their linear stability analysis. 69 Corticothalamic model 70 The corticothalamic system can be described by a continuum approach at the 71 macroscopic level. Large-scale neural activities are determined by interactions between 72 several neural populations, notably excitatory and inhibitory cortical neurons and 73 thalamus, including reticular and relay nuclei.…”

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confidence: 99%

“…(iv) Lesions and pharmacological manipulations of the basal ganglia (BG) and 486 neuromodulator pathways affect SWDs [66,67]. The effect of BG has been proposed to 487 be important for maintaining absence seizures over several tens of seconds by the 488 dynamical loop of the BG-thalamo-cortical network [68], which also provides a 489 modulation site and an intervention pathway to prevent absence seizures [69,70]. So it 490 is essential to investigate the effect of BG modulation on the suppression, localization, 491 and generalization of focal activity.…”

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confidence: 99%

Unified Analysis of Global and Focal Aspects of Absence Epilepsy via Neural Field Theory of the Corticothalamic System

Yang

Robinson

2018

Preprint

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A physiology-based corticothalamic model is investigated with focal spatial heterogeneity, to unify global and focal aspects of absence epilepsy. Numerical and analytical calculations are employed to investigate the emergent spatiotemporal dynamics induced by focal activity as well as their underlying dynamical mechanisms. The spatiotemporal dynamics can be categorized into three scenarios: suppression, localization, and generalization of the focal activity, as summarized from a phase diagram vs. focal width and characteristic axon range. The corresponding temporal frequencies and spatial extents of wave activity during seizure generalization and localization agree well with experimental observations of global and focal aspects of absence epilepsy, respectively. The emergent seizure localization provide a biophysical explanation of the temporally higher frequency but spatially more localized cortical waves observed in genetic rat models that display characteristics of human absence epilepsy. Predictions are also presented for further experimental test. Author SummaryAbsence epilepsy is characterized by a sudden paroxysmal loss of consciousness accompanied by oscillatory activity propagating over many brain areas. Although primary generalized absence seizures are supported by the global corticothalamic system, converging experimental evidence supports a focal theory of absence epilepsy. Here we propose a dynamical mechanism to unify the global and focal aspects of absence epilepsy, with focal absence seizures associated with seizure localization, and the global ones associated with seizure generalization. Our corticothalamic model is used to investigate how seizure rhythms and spatial extents are related in these two different aspects of absence epilepsy. The results account for the difference of the experimentally observed seizure rhythms and spatial extents between humans and genetic rat models, which has previously been used to argue against the validity of such rats as animal models of absence epilepsy in humans.

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

Cited by 67 publications

References 62 publications

Stimulus-induced Epileptic Spike-Wave Discharges in Thalamocortical Model with Disinhibition

Stimulus-induced Epileptic Spike-Wave Discharges in Thalamocortical Model with Disinhibition

Controlling absence seizures by tuning activation level of the thalamus and striatum

Unified Analysis of Global and Focal Aspects of Absence Epilepsy via Neural Field Theory of the Corticothalamic System

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