title: Changes in long-range connectivity and neuronal reorganization in partial cortical deafferentation model of epileptogenesis.
abstract: Severe brain injuries can trigger epileptogenesis, a latent period that eventually leads to epilepsy. Previous studies have demonstrated that changes in local connectivity between cortical neurons are a part of the epileptogenic processes. In the present study we aimed to investigate whether changes in long-range connectivity are also involved in epileptogenesis. We performed a large unilateral transection (undercut) of the white matter below the suprasylvian gyrus in cats. After about 2 months, we either injected retrograde tracer (cholera toxin, sub-unit B, CTB) or performed Golgi staining. We analyzed distribution of retrogradely labeled neurons, counted dendritic spines in the neocortex (Golgi staining), and analyzed dendritic orientation in control conditions and after the injury. We found a significant increase in the number of detected cells at the frontal parts of the injured hemisphere, which suggests that the process of axonal sprouting occurs in the deafferented area. The increase in the number of retrogradely stained neurons was accompanied with a significant decrease in neocortical spine density in the undercut area, a reduction in vertical and an increase in horizontal orientation of neuronal processes. The present study shows global morphological changes underlying epileptogenesis. An increased connectivity in the injured cortical regions accompanied with a decrease in spine density suggests that excitatory synapses might be formed on dendritic shafts, which probably contributes to the altered neuronal excitability that was described in previous studies on epileptogenesis.
authors.affiliation: Centre de recherche de l'Institut universitaire en santé mentale de Québec (CRIUSMQ), Université Laval, Québec G1J 2G3, Canada. Electronic address: magda.kusmierczak.1@ulaval.ca.
authors.forename: M
authors.initials: M
authors.lastname: Kuśmierczak
authors.affiliation: Centre de recherche de l'Institut universitaire en santé mentale de Québec (CRIUSMQ), Université Laval, Québec G1J 2G3, Canada. Electronic address: francis.lajeunesse.1@ulaval.ca.
authors.forename: F
authors.initials: F
authors.lastname: Lajeunesse
authors.affiliation: Centre de recherche de l'Institut universitaire en santé mentale de Québec (CRIUSMQ), Université Laval, Québec G1J 2G3, Canada. Electronic address: Laszlo.Grand@libd.org.
authors.forename: L
authors.initials: L
authors.lastname: Grand
authors.affiliation: Centre de recherche de l'Institut universitaire en santé mentale de Québec (CRIUSMQ), Université Laval, Québec G1J 2G3, Canada; Department of Psychiatry and Neuroscience, Université Laval, Québec G1V 0A6, Canada. Electronic address: Igor.Timofeev@phs.ulaval.ca.
authors.forename: I
authors.initials: I
authors.lastname: Timofeev
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology*; D002415:Cats; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D002772:Cholera Toxin / Q000378:metabolism; D049229:Dendritic Spines / Q000648:ultrastructure; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007839:Functional Laterality; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D012038:Regeneration / Q000502:physiology*; D016622:Silver Staining
chemical_list: D002772:Cholera Toxin
keywords: cholera toxin; epileptogenesis; retrograde staining; sprouting