Synaptic Regulation of Immediate Early Gene Expression in Primary Cultures of Cortical Neurons

T. H. Murphy, P. F. Worley, Y. Nakabeppu, B. Christy, J. Gastel, J. M. Baraban

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Abstract: Neuronal stimulation can rapidly activate several immediate early genes that code for transcription factors. We have used primary cortical cultures to study the regulation of four of these genes, c‐fos, c‐jun, jun‐B, and zif268. Im‐munocytochemical studies with antibodies to Jun‐B, c‐Jun, and c‐Fos demonstrate intense staining in the nuclei of a subset of cortical neurons in mature cultures (21–25 days in vitro) but not young cultures (3–7 days in vitro). To assess whether this immunoreactivity may be induced by spontaneous synaptic activity that develops with a similar profile, we examined the effects of agents that reduce this synaptic activity. Tetrodotoxin or N‐methyl‐d‐aspartate receptor antagonists suppress basal immunoreactivity to Jun‐B and c‐Fos, but not c‐Jun, indicating that the basal level of c‐Jun expression is not dependent on electrical activity. Pierotoxin, an agent that increases synaptic excitation indirectly by blocking inhibitory synaptic currents mediated by γ‐aminobutyric acidA receptors, markedly increases the percentage of neurons displaying immunoreactivity to c‐Fos, c‐Jun, Jun‐B, and Zif268. Northern analysis suggests that the increases in immunostaining induced by picrotoxin are secondary to a rapid increase in mRNA for these proteins. These findings provide evidence for rapid transcriptional regulation of immediate early genes in cortical neurons by synaptic activity.

Original languageEnglish (US)
Pages (from-to)1862-1872
Number of pages11
JournalJournal of Neurochemistry
Volume57
Issue number6
DOIs
StatePublished - Dec 1991
Externally publishedYes

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Keywords

  • Murphy T. H. et al. Synaptic regulation of immediate early gene expression in primary cultures of cortical neurons.
  • N‐Methyl‐d‐aspartate—Transcription factor—Cortex—c‐Fos—c‐Jun—Plasticity

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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