Visually or auditorily induced seizures involve the activation of nonhippocampal brain areas and hippocampal removal does not alleviate seizures in a mouse model of temporal lobe epilepsy

OBJECTIVE: Several studies have attributed epileptic activities in temporal lobe epilepsy (TLE) to the hippocampus; however, the participation of nonhippocampal neuronal networks in the development of TLE is often neglected. Here, we sought to understand how these nonhippocampal networks are involved in the pathology that is associated with TLE disease. METHODS: A kainic acid (KA) model of temporal lobe epilepsy was induced by injecting KA into dorsal hippocampus of C57BL/6J mice. Network activation after spontaneous seizure was assessed using c-Fos expression. Protocols to induce seizure using visual or auditory stimulation were developed, and seizure onset zone (SOZ) and frequency of epileptic spikes were evaluated using electrophysiology. The hippocampus was removed to assess seizure recurrence in the absence of hippocampus. RESULTS: Our results showed that cortical and hippocampal epileptic networks are activated during spontaneous seizures. Perturbation of these networks using visual or auditory stimulation readily precipitates seizures in TLE mice; the frequency of the light-induced or noise-induced seizures depends on the induction modality adopted during the induction period. Localization of SOZ revealed the existence of cortical and hippocampal SOZ in light-induced and noise-induced seizures, and the development of local and remote epileptic spikes in TLE occurs during the early stage of the disease. Importantly, we further discovered that removal of the hippocampi does not stop seizure activities in TLE mice, revealing that seizures in TLE mice can occur independent of the hippocampus. SIGNIFICANCE: This study has shown that the network pathology that evolves in TLE is not localized to the hippocampus; rather, remote brain areas are also recruited. The occurrence of light-induced or noise-induced seizures and epileptic discharges in epileptic mice is a consequence of the activation of nonhippocampal brain areas. This work therefore demonstrates the fundamental role of nonhippocampal epileptic networks in generating epileptic activities with or without the hippocampus in TLE disease.