Robust dual dynamics of ictogenesis in temporal lobe seizures in vivo

Ictogenesis is a pivotal yet poorly understood aspect of epilepsy. Using two-photon calcium imaging, we simultaneously recorded excitatory CA1 pyramidal neurons (PNs) and inhibitory parvalbumin and somatostatin interneurons (INs) to examine seizure initiation dynamics in acute and chronic temporal lobe epilepsy models in vivo. Acute seizures exhibited two initiation patterns: INs-first and simultaneous PNs-INs activation, while chronic spontaneous seizures followed only the latter. Chemogenetic and optogenetic experiments further supported dual initiation dynamics, with seizures arising from either PNs or INs activation. At the onset of seizures, synchronization of INs exceeded that of PNs. The recruitment rank order of PNs, and to a lesser extent INs, remained highly consistent across seizures, indicating a stereotyped, robust initiation pathway for seizure initiation. These findings indicate seizures can emerge via two distinct yet stable pathways, reflecting dynamic but stereotyped initiation patterns shaped by excitatory-inhibitory interactions within epileptic networks.