title: Early-life seizures produce lasting alterations in the structure and function of the prefrontal cortex.
abstract: Early-life seizures (ELS) are associated with long-term behavioral disorders including autism and ADHD, suggesting that frontal lobe structures may be permanently affected. We tested whether ELS produce structural alterations in the prefrontal cortex (PFC) and impair PFC-mediated function using an operant task of behavioral flexibility in rats. Adult rats that had been exposed to 75 flurothyl seizures during postnatal days 1-10 showed decreased behavioral flexibility in the task compared to controls over multiple behavioral sessions, measured as a lever preference asymmetry (p<0.001) and a decreased efficiency of attaining food rewards (p<0.05). ELS rats also showed an increased thickness of the PFC (p<0.01), primarily attributed to layer V (p<0.01) with no differences in cell density. These structural changes correlated with lever preference behavioral impairments (p<0.05). This study demonstrates that the consequences of ELS extend to the PFC, which may help explain the high prevalence of comorbid behavioral disorders following ELS.
authors.affiliation: Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Hanover, NH 03756, USA.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Kleen
authors.forename: Alexandre
authors.initials: A
authors.lastname: Sesqué
authors.forename: Edie X
authors.initials: EX
authors.lastname: Wu
authors.forename: Forrest A
authors.initials: FA
authors.lastname: Miller
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Hernan
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Holmes
authors.forename: Rod C
authors.initials: RC
authors.lastname: Scott
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003216:Conditioning, Operant / Q000502:physiology*; D004195:Disease Models, Animal; D004569:Electroencephalography; D005481:Flurothyl / Q000633:toxicity; D008297:Male; D017397:Prefrontal Cortex / Q000473:pathology* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000473:pathology*
chemical_list: D005481:Flurothyl