title: Experimental febrile seizures induce age-dependent structural plasticity and improve memory in mice.
abstract: Population-based studies have demonstrated that children with a history of febrile seizure (FS) perform better than age-matched controls at hippocampus-dependent memory tasks. Here, we report that FSs induce two distinct structural reorganizations in the hippocampus and bidirectionally modify future learning abilities in an age-dependent manner. Compared with age-matched controls, adult mice that had experienced experimental FSs induced by hyperthermia (HT) on postnatal day 14 (P14-HT) performed better in a cognitive task that requires dentate granule cells (DGCs). The enhanced memory performance correlated with an FS-induced persistent increase in the density of large mossy fiber terminals (LMTs) of the DGCs. The memory enhancement was not observed in mice that had experienced HT-induced seizures at P11 which exhibited abnormally located DGCs in addition to the increased LMT density. The ectopic DGCs of the P11-HT mice were abolished by the diuretic bumetanide, and this pharmacological treatment unveiled the masked memory enhancement. Thus, this work provides a novel basis for age-dependent structural plasticity in which FSs influence future brain function.
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tao
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Ichikawa
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Matsuki
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ikegaya
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan. Electronic address: rkoyama@mol.f.u-tokyo.ac.jp.
authors.forename: R
authors.initials: R
authors.lastname: Koyama
mesh_terms: D000375:Aging; D000818:Animals; D002034:Bumetanide / Q000378:metabolism; D004195:Disease Models, Animal; D005334:Fever / Q000150:complications*; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D008568:Memory / Q000502:physiology*; D051379:Mice; D055495:Neurogenesis / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D012640:Seizures / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D002034:Bumetanide
keywords: dentate gyrus; febrile seizure; hippocampus; memory; structural plasticity