Abstract
Exposure to repetitive seizures is known to promote convulsions which depend on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by a 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 inter-stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures always appeared in frontal cortex, but only at the fourth stimulation they involved the hippocampus, suggesting the establishment of an epileptogenic process. Duration of seizure non-motor component 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 indicate a predominant role of amygdala in promoting progressively more severe convulsions as well as the late recruitment of the hippocampus in the seizure spread. We propose that the repeated 6-Hz corneal stimulation model may be used to investigate some mechanisms of epileptogenesis and to test putative antiepileptogenic drugs.
Highlights
The 6-Hz corneal stimulation model was introduced in early fifties [1] to screen new anticonvulsants [2]
Fast Fourier transformation of EEG traces recorded by epidural electrode implanted in frontal cortex confirmed that power spectrum of post-ictal depression was characterized by a peak, within low frequency range (Fig 1B), significantly smaller than the power peak obtained for ictal events (P
In order to determine which brain structures were activated by repeated 6-Hz corneal stimulation, we evaluated FosB/ΔFosB expression in hippocampal (CA1, CA3, dentate gyrus (DG), Sub) and cortical (EC, PER, piriform cortex (PIR)) regions
Summary
The 6-Hz corneal stimulation model was introduced in early fifties [1] to screen new anticonvulsants [2]. This model has been recently rediscovered to test alternative approaches for drugresistant seizures [3]. When compared with other models based on electrical stimulation, the 6-Hz paradigm is characterized by the induction of minimally convulsive or non-convulsive seizures with automatized behaviors, defined as “psychomotor seizures” [1,3,6]. Animals develop generalized tonic-clonic seizures with the 6-Hz protocol, whereas tonic seizures are predictably obtained in other models based on electrical stimulation, such as the maximal electroshock seizure model [7]
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