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

✍ Scribed by Ramiro Freudenthal; Arturo Romano; Aryeh Routtenberg

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 552 KB
• Volume: 14
• Category: Article
• ISSN: 1050-9631
• DOI: 10.1002/hipo.20020

✦ Synopsis

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. © 2004 Wiley‐Liss, Inc.