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Abstract
BackgroundEpilepsy, 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 ResultsNeuronal 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.ConclusionOur 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.
Highlights
Cortical seizure onset results presumably from an imbalance of neuronal excitation and inhibition toward the synchronous overexcitation of network neurons [1,2,3,4,5]
Our study supports a notion that activity-induced spontaneous spikes in GABAergic neurons may be an endogenous mechanism for seizure self-termination
A portion of inhibitory neurons is upregulated for activity-induced spontaneous spikes in seizureonset tissue
Summary
Cortical seizure onset results presumably from an imbalance of neuronal excitation and inhibition toward the synchronous overexcitation of network neurons [1,2,3,4,5]. Because seizure activity is an automatic termination, there may be endogenous mechanisms for seizure self-termination in the brain [9, 10], such as the functional upregulation of GABAergic neurons, to arrest epilepsy [10, 11]. In terms of a role of GABAergic neurons in seizure termination, a portion of these neurons with functional upregulation emerge in the temporal lobe cortices of temporal lobe epilepsy (TLE) patients, which facilitates www.impactjournals.com/oncotarget seizure self-termination [11]. There are two strategies address this hypothesis, i.e., molecular biology to upregulate AISS-generated GABAergic neurons in their portions, spiking abilities or both as well as computational modeling to simulate whether an upregulation of AISSgenerated GABAergic cells arrests seizure activity. We aim to examine the role of activity-induced spontaneous spikes at GABAergic neurons as an endogenous mechanism in the seizure self-termination
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