Oncotarget

Research Papers: Pathology:

Activity-induced spontaneous spikes in GABAergic neurons suppress seizure discharges: an implication of computational modeling

Wei Lu, Jing Feng, Bo Wen, Kewei Wang and Jin-Hui Wang _

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Oncotarget. 2017; 8:32384-32397. https://doi.org/10.18632/oncotarget.15660

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Abstract

Wei Lu1,*, Jing Feng1,2,*, Bo Wen2, Kewei Wang1 and Jin-Hui Wang1,2,3

1 Qingdao University, School of Pharmacy, Qingdao, Shandong, China

2 State Key lab for Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

3 University of Chinese Academy of Sciences, Beijing, China

* These authors have contributed to this work equally

Correspondence to:

Jin-Hui Wang, email:

Kewei Wang, email:

Keywords: Epilepsy, spikes, neuron, synaptic transmission and GABA, Pathology Section

Received: January 05, 2017 Accepted: February 13, 2017 Published: February 23, 2017

Abstract

Background: Epilepsy, a prevalent neurological disorder, appears self-termination. The endogenous mechanism for seizure self-termination remains to be addressed in order to develop new strategies for epilepsy treatment. We aim to examine the role of activity-induced spontaneous spikes at GABAergic neurons as an endogenous mechanism in the seizure self-termination.

Methods and Results: Neuronal spikes were induced by depolarization pulses at cortical GABAergic neurons from temporal lobe epilepsy patients and mice, in which some of these neurons fired activity-induced spontaneous spikes. Neural networks including excitatory and inhibitory neurons were computationally constructed, and their functional properties were based on our studies from whole-cell recordings. With the changes in the portion and excitability of inhibitory neurons that generated activity-induced spontaneous spike, the efficacies to suppress synchronous seizure activity were analyzed, such as its onset time, decay slope and spike frequency. The increases in the proportion and excitability of inhibitory neurons that generated activity-induced spontaneous spikes effectively suppressed seizure activity in neural networks. These factors synergistically strengthened the efficacy of seizure activity suppression.

Conclusion: Our study supports a notion that activity-induced spontaneous spikes in GABAergic neurons may be an endogenous mechanism for seizure self-termination. A potential therapeutic strategy for epilepsy is to upregulate the cortical inhibitory neurons that generate activity-induced spontaneous spikes.


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