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Synaptic Regulation of Immediate Early Gene Expression in Primary Cultures of Cortical Neurons
Author(s) -
Murphy T. H.,
Worley P. F.,
Nakabeppu Y.,
Christy B.,
Gastel J.,
Baraban J. M.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb06396.x
Subject(s) - immediate early gene , picrotoxin , biology , neurotransmission , neuroscience , gene expression , immunostaining , receptor , c fos , premovement neuronal activity , tetrodotoxin , microbiology and biotechnology , endocrinology , gene , immunohistochemistry , biochemistry , immunology , gabaa receptor
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 acid A 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.