Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation

Andrew J. Cole, David W. Saffen, Jay M. Baraban, Paul F. Worley

Research output: Contribution to journalArticlepeer-review

874 Scopus citations


RECENT studies in invertebrates indicate that a rapid genomic response to neuronal stimulation has a critical role in long-term changes in synaptic efficacy. Because several of the genes (immediately early genes; IEGs) that respond rapidly to growth factor stimulation of vertebrate cells in vitro are also activated by neuronal stimulation in vivo, attention has focused on the possibility that they play a part in synaptic plasticity in vertebrate nervous systems. Four IEGs thought to encode transcription factors, zif/2685 (also termed Egr-114, NGFI-A15, Krox 2416), c-fos17, c-jun18, and jun-B7 are rapidly induced in the brain by seizure activity, and we have now studied the induction of these genes in a well-characterized model of synaptic plasticity in the vertebrate brain-long-term potentiation (LTP) of the perforant path-granule cell (pp-gc) synapse in vivo. We found that high-frequency (but not low-frequency) stimulation of the pp-gc synapse markedly increases zif/268 messenger RNA (mRNA) levels in the ipsilateral granule cell neurons; mRNA of c-fos, c-jun and jun-B is less consistently increased. The stimulus frequency and intensity required to induce LTP, which is also seen only ipsilaterally, and both responses are blocked by NMDA-receptor antagonists as well as by convergent synaptic inhibitory inputs already known to block LTP. Accordingly, zif/268 mRNA levels and LTP seem to be regulated by similar synaptic mechanisms.

Original languageEnglish (US)
Pages (from-to)474-476
Number of pages3
Issue number6233
StatePublished - 1989

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