Induction of c-fos mRNA by kindled seizures: Complex relationship with neuronal burst firing

D. M. Labiner, L. S. Butler, Z. Cao, D. A. Hosford, C. Shin, J. O. McNamara

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205 Scopus citations


Expression of the immediate-early gene c-fos has been advanced as a marker of neuronal activity in the adult nervous system. We sought to test the validity of c-fos mRNA expression as a marker of neuronal activity during seizures and to elucidate specific neurotransmitter receptors whose activation was necessary for seizure-evoked c-fos mRNA expression. We correlated c-fos mRNA expression, measured with in situ hybridization, with kindled seizure-induced firing of hippocampal dentate granule cells or substantia nigra pars compacta and pars reticulata neurons. We found that the occurrence of seizure-evoked synchronous action potentials during the seizure exhibited a perfect qualitative correlation with the presence of c-fos mRNA expression in the granule cells 30 min following the seizure (Fisher's exact test, p = 0.002). However, there was no quantitative correlation between the number of seizure-induced population action potentials and the magnitude of c-fos mRNA expression in the granule cells. In the substantia nigra, where neuronal populations have previously been demonstrated to exhibit synchronous firing during kindled seizures, no induction of c-fos mRNA was detected in either pars compacta or pars reticulata. Pretreatment with antagonists of the NMDA subtype of glutamate receptor selectively and markedly decreased seizure-induced c-fos mRNA expression in the dentate granule cells, despite increasing the number of granule cell population action potentials. These findings illustrate the complexity of the relationship between c-fos induction and neuronal burst firing during kindled seizures. We caution that c-fos mRNA expression is not a simple marker of neuronal activity. We suggest that seizure-induction of c-fos mRNA expression may correlate better with sustained neuronal depolarization and subsequent rise of intracellular calcium evoked by multiple factors, one of which is NMDA receptor activation.

Original languageEnglish (US)
Pages (from-to)744-751
Number of pages8
JournalJournal of Neuroscience
Issue number2
StatePublished - 1993


  • C-fos
  • Dentate granule cells
  • Epilepsy
  • Kindling
  • NMDA
  • Neuronal activity
  • Seizure
  • Substantia nigra

ASJC Scopus subject areas

  • General Neuroscience


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