Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation.
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.
Cole
A J
AJ
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Saffen
D W
DW
Baraban
J M
JM
Worley
P F
PF
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D004558:Electric Stimulation; D007839:Functional Laterality; D005786:Gene Expression Regulation; D005796:Genes; D006624:Hippocampus / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D014157:Transcription Factors