Spatiotemporal induction of immediate early genes in the rat brain after limbic seizures: effects of NMDA receptor antagonist MK-801

Abstract

Fos, jun and krox belong to multigene families coding for transcription factors. These cellular immediate early genes (IEGs) are thought to be involved in coupling neuronal excitation to changes of target gene expression. Immunocytochemistry with specific antisera was used to assess regional levels of six IEG-encoded proteins (c-Fos, Fos B, Krox-24, c-Jun, Jun B, Jun D) in the rat forebrain after kainic acid-induced limbic seizures. The results demonstrate a complex spatial pattern of IEG induction and/or suppression in limbic and non-limbic structures. The sequence of induction within hippocampal subpopulations was identical for all IEGs investigated, following the order dentate gyrus, CA1 and CA3, and irrespective of different temporal profiles for individual transcription factors. Since Fos and Jun proteins act via homo- and heterodimer complexes at specific DNA sites, our data imply that the postictal combinatorial changes of these dimers allow a sequential and differential regulation of target gene expression in specific forebrain regions. Pretreatment with the non-competitive NMDA receptor antagonist MK-801 did not affect kainate-induced expression of IEGs in the limbic system, indicating that IEG induction in these regions is mediated by high-affinity kainate and AMPA receptors rather than NMDA receptors. In contrast, MK-801 abolished IEG induction in the somatosensory cortex and striatum, suggesting that IEG expression in non-limbic neurons occurs transsynaptically and is mediated by NMDA receptors.