C-Fos mapping and EEG characteristics of multiple mice brain regions in pentylenetetrazol-induced seizure mice model

ABSTRACT

Purpose: To confirm different local brain activities characterized in pentylenetetrazol (PTZ)-induced seizure model.

Methods: we induced seizure response by a single dose of PTZ injection (45 mg/kg, i.p.). Local activity was recorded in different brain regions by EEG in time and c-Fos staining at different time points (0.5 h, 1 h, 2 h, 4 h) after PTZ treatment.

Results: EEG recordings showed distinctive features of activation in different brain areas. With the aggravation of behavioral manifestations of seizures, the frequency and amplitude of the discharges on EEG were increasing gradually. The epileptic response on EEG immediately ended after reaching the maximum stage of seizures, followed by a short period of suppression. The labeling of c-Fos was enhanced in the medial prefrontal cortex, the piriform cortex, the amygdala, hippocampal CA1, CA3 and dentate gyrus, but inapparent in the striatum. The most potent changes in c-Fos were observed in cortex, amygdala nuclei, and dentate gyrus. EEG and c-Fos immunolabeling in neuronal activation showed discrepancies in the striatum. For each brain region, the maximum c-Fos labeling was observed at 2 h after injection and diminished at 4 h. The level of c-Fos immunoreactivity was even lower than the control group, which was accompanied by increased labeling of parvalbumin neurons (PVNs).

Conclusions: These findings validated PTZ-induced seizure as a seizure model with a specific spatial-temporal profile. Neuronal activity was enhanced and then subsequently inhibited during seizure evolution.

Abbreviations: AEDs: anti-epileptic drugs; AF: Alexa Fluor; CA1: Cornu Ammonis area 1; CA3: Cornu Ammonis area 3; DAB, 3: 3P-diaminobenzidine; DAPI: 4‘,6-diamidino-2-phenylindole; DG: dentate gyrus; EEG: electroencephalogram; GABA: gamma-aminobutyric acid; IEG: immediate early gene; mPFC: medial prefrontal cortex; NAc: nucleus accumbens; PB: phosphate buffer; PBS: phosphate buffered saline; PBST: phosphate buffered saline with Tween; PFA, paraformaldehyde; PTZ: pentylenetetrazol; PVN: parvalbumin neuron; ROI: regions of interest; SE: status epilepticus.