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Open Access Highly Accessed Research article

NF-κB p50 subunit knockout impairs late LTP and alters long term memory in the mouse hippocampus

Kensuke Oikawa1, Gary L Odero1, Eric Platt1, Melanie Neuendorff1, Avril Hatherell1, Michael J Bernstein2 and Benedict C Albensi134*

Author Affiliations

1 Div’n. of Neurodegenerative Disorders, St. Boniface Hospital Research, Winnipeg, MB, Canada

2 Dept. of Psychological and Social Sciences, Pennsylvania State University, Abington, PA, USA

3 Dept. of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, MB, Canada

4 St. Boniface Research Ctr., 351 Tache Ave. / R4050, Winnipeg, MB, R2H 2A6, Canada

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BMC Neuroscience 2012, 13:45  doi:10.1186/1471-2202-13-45

Published: 3 May 2012

Abstract

Background

Nuclear factor kappa B (NF-κB) is a transcription factor typically expressed with two specific subunits (p50, p65). Investigators have reported that NF-κB is activated during the induction of in vitro long term potentiation (LTP), a paradigm of synaptic plasticity and correlate of memory, suggesting that NF-κB may be necessary for some aspects of memory encoding. Furthermore, NF-κB has been implicated as a potential requirement in behavioral tests of memory. Unfortunately, very little work has been done to explore the effects of deleting specific NF-κB subunits on memory. Studies have shown that NF-κB p50 subunit deletion (p50−/−) leads to memory deficits, however some recent studies suggest the contrary where p50−/− mice show enhanced memory in the Morris water maze (MWM). To more critically explore the role of the NF-κB p50 subunit in synaptic plasticity and memory, we assessed long term spatial memory in vivo using the MWM, and synaptic plasticity in vitro utilizing high frequency stimuli capable of eliciting LTP in slices from the hippocampus of NF-κB p50−/− versus their controls (p50+/+).

Results

We found that the lack of the NF-κB p50 subunit led to significant decreases in late LTP and in selective but significant alterations in MWM tests (i.e., some improvements during acquisition, but deficits during retention).

Conclusions

These results support the hypothesis that the NF-κ p50 subunit is required in long term spatial memory in the hippocampus.

Keywords:
Hippocampus; NF-kappa B; Water maze; LTP; Transcription; Memory