Essential role of the fosB gene in molecular, cellular, and behavioral actions of chronic electroconvulsive seizures

Noboru Hiroi, Gerard J. Marek, Jennifer R. Brown, Hong Ye, Frederic Saudou, Vidita A. Vaidya, Ronald S. Duman, Michael E. Greenberg, Eric J. Nestler

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

The role of Fos-like transcription factors in neuronal and behavioral plasticity has remained elusive. Here we demonstrate that a Fos family member protein plays physiological roles in the neuronal, electrophysiological, and behavioral plasticity associated with repeated seizures. Repeated electroconvulsive seizures (ECS) induced isoforms of ΔFosB in frontal cortex, an effect that was associated with increased levels of the NMDA receptor 1 (NMDAR1) glutamate receptor subunit. Induction of ΔFosB and the upregulation of NMDAR1 occurred within the same neurons in superficial layers of neocortex. Activator protein-1 (AP-1) complexes composed of ΔFosB were bound to a consensus AP-1 site in the 5'-promoter region of the NMDAR1 gene. The upregulation of NMDAR1 was absent in mice with a targeted disruption of the fosB gene. In addition, repeated ECS treatment caused progressively shorter motor seizures (tolerance) in both rats and wild-type mice, as well as reduced NMDA-induced inward currents in pyramidal neurons from superficial layers of the neocortex of wild-type mice. These behavioral and electrophysiological effects were also significantly attenuated in fosB mutant mice. These findings identify fosB gene products as transcription factors critical for molecular, electrophysiological, and behavioral adaptations to motor seizures.

Original languageEnglish (US)
Pages (from-to)6952-6962
Number of pages11
JournalJournal of Neuroscience
Volume18
Issue number17
DOIs
StatePublished - Sep 1 1998

Keywords

  • AP-1
  • C- Fos
  • Cerebral cortex
  • Depression
  • ECS
  • Epilepsy
  • FRA
  • FosB
  • JunD
  • NMDA receptor
  • Neural plasticity
  • Seizure
  • Transcription factor
  • ΔFosB

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Hiroi, N., Marek, G. J., Brown, J. R., Ye, H., Saudou, F., Vaidya, V. A., Duman, R. S., Greenberg, M. E., & Nestler, E. J. (1998). Essential role of the fosB gene in molecular, cellular, and behavioral actions of chronic electroconvulsive seizures. Journal of Neuroscience, 18(17), 6952-6962. https://doi.org/10.1523/jneurosci.18-17-06952.1998