Induction of c-fos mRNA by kindled seizures: complex relationship with neuronal burst firing.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina 27710.
D M
DM
Labiner
L S
LS
Butler
Z
Z
Cao
D A
DA
Hosford
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C
Shin
J O
JO
McNamara
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists; D015870:Gene Expression; D016762:Genes, fos; D006624:Hippocampus / Q000503:physiopathology; D017403:In Situ Hybridization; D007696:Kindling, Neurologic; D008297:Male; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D012640:Seizures / Q000503:physiopathology*; D013378:Substantia Nigra / Q000503:physiopathology
D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate