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

Nature. 1989 Aug 10;340(6233):474-6. doi: 10.1038/340474a0.


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/268 (also termed Egr-1, NGFI-A, Krox 24), c-fos, c-jun, and jun-B 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 pathgranule 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 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 LTP. Accordingly, zif/268 mRNA levels and LTP seem to be regulated by similar synaptic mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Afferent Pathways / physiology
  • Animals
  • Electric Stimulation
  • Functional Laterality
  • Gene Expression Regulation*
  • Genes*
  • Hippocampus / physiology*
  • Neurons / physiology*
  • RNA, Messenger / genetics*
  • Rats
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / physiology*
  • Synapses / physiology*
  • Transcription Factors / genetics
  • Transcription, Genetic


  • RNA, Messenger
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • Transcription Factors