Abstract
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 language | English (US) |
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Pages (from-to) | 744-751 |
Number of pages | 8 |
Journal | Journal of Neuroscience |
Volume | 13 |
Issue number | 2 |
State | Published - 1993 |
Externally published | Yes |
Keywords
- C-fos
- Dentate granule cells
- Epilepsy
- Kindling
- NMDA
- Neuronal activity
- Seizure
- Substantia nigra
ASJC Scopus subject areas
- General Neuroscience