Null mutation of c-fos impairs structural and functional plasticities in the kindling model of epilepsy.

Journal Article (Journal Article)

It has been suggested that expression of the immediate early gene c-fos links fleeting changes in neuronal activity to lasting modifications of neuronal structure and function in the mammalian nervous system. To test this idea, we examined behavioral and electrophysiological indices of kindling development and kindling-induced sprouting of hippocampal granule cell axons in wild-type (+/+), heterozygous (+/-), and homozygous (-/-) mice carrying a null mutation of c-fos. The rate of kindling development was significantly attenuated in -/- compared with +/+ mice, as evidenced by both electrophysiological and behavioral measures. Kindling-induced granule cell axon sprouting as measured by the Timm stain was also attenuated in homozygous null mutants compared with +/+ mice, with an intermediate effect in +/- mice. The impairment of kindling-induced axonal sprouting in the null mutants could not be attributed to either detectable loss of dentate hilar neurons or reduced activation of the dentate granule cells by seizures. Instead, our data are consistent with the hypothesis that the null mutation of c-fos attenuates a pathological activity-determined functional plasticity (kindling development) as well as a structural plasticity (mossy fiber reorganization). We favor the hypothesis that this "fos-less phenotype" is attributable to impaired seizure-induced transcriptional activation of one or more growth-related genes.

Full Text

Duke Authors

Cited Authors

  • Watanabe, Y; Johnson, RS; Butler, LS; Binder, DK; Spiegelman, BM; Papaioannou, VE; McNamara, JO

Published Date

  • June 15, 1996

Published In

Volume / Issue

  • 16 / 12

Start / End Page

  • 3827 - 3836

PubMed ID

  • 8656277

Pubmed Central ID

  • PMC6578612

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.16-12-03827.1996


  • eng

Conference Location

  • United States