Gene expression of the transcription factor NF-κB in hippocampus: Regulation by synaptic activity

Peter J. Meberg, Walter R. Kinney, Eric G. Valcourt, Aryeh Routtenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

187 Scopus citations

Abstract

NF-κB is a potent transcriptional activator that resides in latent farm in the cytoplasm complexed to its inhibitor IκB. Phosphorylation of IκB by protein kinase C (PKC) releases NF-κB, enabling its translocation to the nucleus. Since PKC can activate NF-κB and PKC is activated by long-term potentiation (LTP), we investigated NF-κB expression after hippocampal LTP induced in vivo. We first described the expression of the NF-κB subunits, p50 and p65, and IκBα mRNAs, in each cell field of the hippocampus. In other brain locations IκBα mRNA exhibited a more selective expression than p50 and p65. We then demonstrated specific NF-κB-like DNA-binding activity in hippocampal whole-cell extracts and in synaptosomes using electrophoretic mobility shift assays by the following criteria: (1) latent binding was revealed after deoxycholate treatment; (2) binding was competed off by unlabeled κB oligonucleotides; and (3) antibodies to either p50 or p65 blocked binding. Since p50 gene expression is auto-regulated by NF-κB, we used its expression as a reporter for NF-κB activity using quantitative in situ hybridization. Both p50 and p65 increased their expression in response to either LTP-inducing or low-frequency control stimulation, although the increase in p65 mRNA levels was greater after LTP than control stimulation. In contrast to p50 and p65, IκBα hybridization levels were not increased, but were inversely correlated with the magnitude of LTP. Since NF-κB subunit gene expression in the hippocampus is increased by augmented synaptic activity, NF-κB activation may contribute to alterations in target gene expression that accompany activity-dependent synaptic plasticity, but only in a combinatorial fashion with other transcription factors.

Original languageEnglish (US)
Pages (from-to)179-190
Number of pages12
JournalMolecular Brain Research
Volume38
Issue number2
DOIs
StatePublished - Jun 1996

Keywords

  • Hippocampus
  • IκB
  • Long-term potentiation
  • NF-κB
  • Protein kinase C
  • Rat
  • Transcription factors
  • mRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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