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

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Abstract

RECENT studies in invertebrates indicate that a rapid genomic response to neuronal stimulation has a critical role in long-term changes in synaptic efficacy1. Because several of the genes (immedi-ately early genes; lEGs) that respond rapidly to growth factor stimulation of vertebrate cells in vitro2-7 are also activated by neuronal stimulation in vivo8-13, attention has focused on the possibility that they play a part in synaptic plasticity in vertebrate nervous systems. Four lEGs thought to encode transcription fac-tors, zif/2685 (also termed Egr-ll4, NGFI-A15, Krox2416), C-fOS17, c-jun18, and jun-B7 are rapidly induced in the brain by seizure activity8,11,13, and we have now studied the induction of these genes in a well-characterized model of synaptic plasticity in the verte-brate brain—-long-term potentiation (LTP) of the perforant path-granule cell (pp-gc) synapse in vivo19. 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 increase zif/268 mRNA levels are similar to those 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 LTP20. Accordingly, zif/268 mRNA levels and LTP seem to be regulated by similar synaptic mechanisms.

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Authors and Affiliations

  1. Departments of Neuroscience, Neurology, Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205, USA

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

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  1. Andrew J. Cole
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  2. David W. Saffen
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  3. Jay M. Baraban
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Cole, A., Saffen, D., Baraban, J. et al. Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation. Nature 340, 474–476 (1989). https://doi.org/10.1038/340474a0

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