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Shape features of epileptic spikes are a marker of epileptogenesis in mice
Author(s) -
Huneau Clément,
Benquet Pascal,
Dieuset Gabriel,
Biraben Arnaud,
Martin Benoît,
Wendling Fabrice
Publication year - 2013
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.12406
Subject(s) - epileptogenesis , epilepsy , neuroscience , clinical neurology , medicine , psychology
Summary Purpose To identify reliable biomarkers for quantitatively assessing the development of epilepsy in brain. Methods In a kainate mouse model of temporal lobe epilepsy, we performed long‐term video–electroencephalography ( EEG ) monitoring (several weeks) of freely moving animals, from kainic acid injection to chronic epileptic stage. Using signal processing techniques, we automatically detected single epileptic spikes ( ES s), and we quantified the evolution of shape features during the epileptogenesis process. Using a computational model of hippocampal activity (neuronal population level), we investigated excitatory‐related and inhibitory‐related parameters involved in morphologic changes of ES s. Key Findings The frequency of ES s increases during epileptogenesis. Regarding shape features, we found that both the initial spike component and the wave component of opposite polarity of ES s gradually increase during epileptogenesis. These very specific alterations of the shape of ES s were reproduced in a computational physiologically relevant neuronal population model. Using this model, we disclosed some key parameters (related to glutamatergic and γ‐aminobutyric acid [ GABA ]ergic synaptic transmission) that explain the shape features of simulated ES s. Of interest, the model predicted that the decrease of GABA ergic inhibition is responsible for the increase of the wave component of ES s. This prediction (at first sight counterintuitive) was verified in both in vivo and in vitro experiments. Finally, from aforementioned electrophysiologic features, we devised a novel and easily computable index (wave area/spike amplitude ratio) indicative of the progression of the disease (early vs. late stage). Significance Results suggest that dendritic inhibition in hippocampal circuits undertake dramatic changes over the latent period. These changes are responsible for observed modifications in the shape of ES s recorded in local field potential ( LFP ) signals. The proposed index may constitute a biomarker of epileptogenesis.