Altered θ coupling between medial entorhinal cortex and dentate gyrus in temporal lobe epilepsy.

Purpose:   Temporal lobe epilepsy is often accompanied by neuron loss and rewiring in the hippocampus. We hypothesized that the interaction of subnetworks of the entorhinal-hippocampal loop between epileptic events should show significant signatures of these pathologic changes.

Methods:   We combined simultaneous recording of local field potentials in entorhinal cortex (EC) and dentate gyrus (DG) in freely behaving kainate-injected mice with histologic analyses and computational modeling.

Key Findings:   In healthy mice, theta band activity was synchronized between EC and DG. In contrast, in epileptic mice, theta activity in the EC was delayed with respect to the DG. A computational neural mass model suggests that hippocampal cell loss imbalances the coupling of subnetworks, introducing the shift.

Significance:   We show that pathologic dynamics in epilepsy encompass ongoing activity in the entorhinal-hippocampal loop beyond acute epileptiform activity. This predominantly affects theta band activity, which links this shift in entorhinal-hippocampal interaction to behavioral aspects in epilepsy.