Epilepsy is a chronic neurological disorder characterized by spontaneous recurrent seizures (SRS) and comorbidities. Kindling through repetitive brief stimulation of a limbic structure is a commonly used model of temporal lobe epilepsy. Particularly, extended kindling over a period up to a few months can induce SRS, which may simulate slowly evolving epileptogenesis of temporal lobe epilepsy. Currently, electroencephalographic (EEG) features of SRS in rodent models of extended kindling remain to be detailed. We explored this using a mouse model of extended hippocampal kindling. Intracranial EEG recordings were made from the kindled hippocampus and unstimulated hippocampal, neocortical, piriform, entorhinal, or thalamic area in individual mice. Spontaneous EEG discharges with concurrent low-voltage fast onsets were observed from the two corresponding areas in nearly all SRS detected, irrespective of associated motor seizures. Examined in brain slices, epileptiform discharges were induced by alkaline artificial cerebrospinal fluid in the hippocampal CA3, piriform and entorhinal cortical areas of extended kindled mice but not control mice. Together, these in vivo and in vitro observations suggest that the epileptic activity involving a macroscopic network may generate concurrent discharges in forebrain areas and initiate SRS in hippocampally kindled mice.

Growing studies indicate that vigilance states and circadian rhythms can influence seizure occurrence in patients with epilepsy and rodent models of epilepsy. Electrical kindling, referred to brief, repeated stimulations of a limbic structure, is a commonly used model of temporal lobe epilepsy. Kindling via the classic protocol lasting a few weeks does not generally induce spontaneous recurrent seizures (SRS), but extended kindling that applies over the course of a few months has shown to induce SRS in several animal species. Kindling-induced SRS in monkeys and cats were observed mainly during resting wakefulness or sleep, but the behavioral activities associated with SRS in rodent models of extended kindling remain unknown. We aimed to add information in this area using a mouse model of extended hippocampal kindling. Middle-aged C57 black mice experienced ≥80 hippocampal stimulations (delivered twice daily) and then underwent continuous 24 h electroencephalography (EEG)-video monitoring for SRS detection. SRS were recognized by EEG discharges and associated motor seizures. The five stages of the modified Racine scale for mice were used to score motor seizure severities. Seizure-preceding behaviors were assessed in a 3 min period prior to seizure onset and categorized as active and inactive. Three main observations emerged from the present analysis. (1) SRS were found to predominantly manifest as generalized (stage 3–5) motor seizures in association with tail erection or Straub tail. (2) SRS occurrences were not significantly altered by the light on/off cycle. (3) Generalized (stage 3–5) motor seizures were mainly preceded by inactive behaviors such as immobility, standing still, or apparent sleep without evident volitional movement. Considering deeper subcortical structures implicated in genesis of tail erection in other seizure models, we postulate that genesis of generalized motor seizures in extended kindled mice may involve deeper subcortical structures. Our present data together with previous findings from post-status epilepticus models support the notion that ambient cage behaviors are strong influencing factors of SRS occurrence in rodent models of temporal lobe epilepsy.