High Theta (4-10 Hz) power as a biomarker of inhibition during epileptogenesis in an animal model of mesial temporal lobe epilepsy.

Theta oscillations (4-10 Hz) are a prominent electrophysiological feature of the hippocampus and are highly dependent on the activity of interneurons and GABAergic signaling. In mesial temporal lobe epilepsy (MTLE), theta oscillations are disrupted in the hippocampus and extra-hippocampal structures. We studied here the time-sensitive changes of hippocampal theta oscillations during epileptogenesis and whether the ictogenic effects induced by the optogenetic stimulation of hippocampal CaMKII-positive principal cells are mirrored by changes in theta oscillations. CaMKII-ChR2 mice (n = 11) were treated with kainic acid (15 mg/kg, i.p.) and recorded from one day before status epilepticus (SE) to 25 days after. In a subgroup of mice (n = 6), optogenetic stimulation (1 Hz, 180 s ON, 220 s OFF) of CaMKII-positive principal cells was performed for 15 days starting 3 h after SE. In non-stimulated, control mice (n = 5), we found that the power of theta oscillations significantly increased during the latent phase and was then followed by a gradual decrease that marked the transition between the latent and chronic epileptic phases. In stimulated animals (n = 6), power of theta oscillations followed a similar time-sensitive pattern. Our findings suggest that time-sensitive changes in theta power are reliable biomarkers of inhibitory interneuron GABAergic function during epileptogenesis.