No evidence of thalamic contribution to seizure generalization

Seizures often originate in an epileptic focus, from where they spread to large areas of the brain. The potential pathways of generalization are of high importance as potential targets of therapeutic intervention. Here, we are testing the hypothesis that seizures generalize from a cortical epileptic focus via thalamic pathways, rather than via direct cortico-cortical connections. Higher-order thalamic nuclei are especially likely to be involved, as they project to large areas of the cortex.We employed an optogenetic acute epilepsy mouse model, where brief (10-15s) stimulation of the layer 6 corticothalamic pathway evoked grand-mal seizure with high probability and repeatability. Animals were traced through several months, with seizures induced daily.Thalamic nuclei (primary and higher-order somatosensory vental posterior and posterior) were inhibited by microinjections of tetrodotoxin, or kainate lesion. So far, neither tetrodotoxin inhibition or kainate lesion of either somatosensory nuclei prevented reliably the generalization of seizures.