Experimental febrile seizures induce age-dependent structural plasticity and improve memory in mice

Neuroscience. 2016 Mar 24:318:34-44. doi: 10.1016/j.neuroscience.2016.01.011. Epub 2016 Jan 12.


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.

Keywords: dentate gyrus; febrile seizure; hippocampus; memory; structural plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Bumetanide / metabolism
  • Disease Models, Animal
  • Fever / complications*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Memory / physiology*
  • Mice
  • Neurogenesis / physiology*
  • Neuronal Plasticity / physiology*
  • Seizures / etiology
  • Seizures / metabolism
  • Seizures / physiopathology*


  • Bumetanide