Transcription factor NF-κB activation after in vivo perforant path LTP in mouse hippocampus

Ramiro Freudenthal, Arturo Romano, Aryeh Routtenberg*

*Corresponding author for this work

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

There is increasing evidence that transcription factors (TFs) play a critical role in maintaining later phases of hippocampal long-term potentiation (LTP). We have been led to study the role in synaptic plasticity of the powerful, yet generally unheralded, NF-κB TF because it may serve as both a signaling molecule after its activation at the synapse and then a transcription initiator upon reaching the nucleus. In the present study, we show that LTP activates NF-κB in the intact mouse hippocampus. Mice were sacrificed 15 min after one of three treatments: tetanization (high-frequency stimulation [HFS]), low-frequency stimulation (LFS), or no stimulated control animals (CT). In a first study, nuclear NF-κB activity from hippocampus was estimated by electrophoretic mobility shift assays (EMSAs). A higher level of hippocampal TF binding to the NF-κB recognition element was found in the HFS group compared with LFS or CT. In a second study, NF-κB activity was evaluated by immunohistochemistry with a specific antibody that recognizes the activated form of NF-κB. This antibody binds to the exposed nuclear location sequence on the p65 subunit of NF-κB consequent to its dissociation from the inhibitory IκB molecule. In the four subfields of hippocampus examined - granule cell layer, hilus of the dentate gyrus, CA3 and CA1 pyramidal fields of the hippocampal gyrus - the highest levels of activated NF-κB, statistically significant in all cases were found after HFS. In certain comparisons, LFS animals also showed significant elevation with respect to CT. These results support the role of NF-κB as part of the synaptic signaling and transcriptional regulation mechanism required in long-term plasticity, emphasizing the combinatorial nature of TF function.

Original languageEnglish (US)
Pages (from-to)677-683
Number of pages7
JournalHippocampus
Volume14
Issue number6
DOIs
StatePublished - Sep 24 2004

Keywords

  • Hippocampus
  • LTP
  • Memory
  • NF-κB
  • NLS
  • p65
  • Perforant path
  • Transcription factor

ASJC Scopus subject areas

  • Neuroscience(all)

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