Involvement of the contralateral hippocampus in ictalâ€like but not interictal epileptic activities in the kainate mouse model of temporal lobe epilepsy

Objective Animal and human studies have shown that the seizureâ€generating region is vastly dependent on distant neuronal hubs that can decrease duration and propagation of ongoing seizures. However, we still lack a comprehensive understanding of the impact of distant brain areas on specific interictal and ictal epileptic activities (e.g., isolated spikes, spike trains, seizures). Such knowledge is critically needed, because all kinds of epileptic activities are not equivalent in terms of clinical expression and impact on the progression of the disease. Methods We used surface highâ€density electroencephalography and multisite intracortical recordings, combined with pharmacological silencing of specific brain regions in the wellâ€known kainate mouse model of temporal lobe epilepsy. We tested the impact of selective regional silencing on the generation of epileptic activities within a continuum ranging from very transient to more sustained and longâ€lasting discharges reminiscent of seizures. Results Silencing the contralateral hippocampus completely suppresses sustained ictal activities in the focus, as efficiently as silencing the focus itself, but whereas focus silencing abolishes all focus activities, contralateral silencing fails to control transient spikes. In parallel, we observed that sustained focus epileptiform discharges in the focus are preceded by contralateral firing and more strongly phaseâ€locked to bihippocampal delta/theta oscillations than transient spiking activities, reinforcing the presumed dominant role of the contralateral hippocampus in promoting longâ€lasting, but not transient, epileptic activities. Significance Altogether, our work provides suggestive evidence that the contralateral hippocampus is necessary for the interictal to ictal state transition and proposes that crosstalk between contralateral neuronal activity and ipsilateral delta/theta oscillation could be a candidate mechanism underlying the progression from short†to longâ€lasting epileptic activities.