Repeated 6-Hz corneal stimulation progressively increases FosB/∆FosB levels in the lateral amygdala and induces seizure generalization to the hippocampus.

Exposure to repetitive seizures is known to promote convulsions which depends on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by the modified 6-Hz corneal stimulation model of psychomotor seizures. Mice received up to 4 sessions of 6-Hz corneal stimulation with fixed current amplitude of 32 mA and an inter-stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures appeared always in frontal cortex, but only at the fourth stimulation they involved the hippocampus. Duration of non-motor seizures progressively decreased after the second session, whereas convulsive seizures remained unchanged. In addition, a more severe seizure phenotype, consisting of tonic-clonic generalized convulsions, was predominant after the second session. Immunohistochemistry and double immunofluorescence experiments revealed a significant increase in neuronal activity occurring in the lateral amygdala after the fourth session most likely due to activity of principal cells. These findings suggest a predominant role of amygdala in promoting progressively more severe convulsions.