title: Repeated 6-Hz Corneal Stimulation Progressively Increases FosB/ΔFosB Levels in the Lateral Amygdala and Induces Seizure Generalization to the Hippocampus.
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.
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Laboratory of Experimental Epileptology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Giordano
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Laboratory of Experimental Epileptology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Vinet
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Laboratory of Experimental Epileptology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Curia
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Laboratory of Experimental Epileptology, University of Modena and Reggio Emilia, Modena, Italy.|Department of Neurosciences, NOCSAE Hospital, AUSL Modena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biagini
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000378:metabolism* / Q000503:physiopathology; D003315:Cornea / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects*; D004567:Electrodes, Implanted; D004569:Electroencephalography; D017029:Epilepsy, Complex Partial / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D004829:Epilepsy, Generalized / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D004830:Epilepsy, Tonic-Clonic / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D051379:Mice; D017628:Microglia / Q000473:pathology; D009415:Nerve Net / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D012720:Severity of Illness Index; D016037:Single-Blind Method; D014741:Video Recording
chemical_list: C483819:Fosb protein, mouse; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos