Abstract
BackgroundNuclear 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+/+).ResultsWe 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).ConclusionsThese results support the hypothesis that the NF-κ p50 subunit is required in long term spatial memory in the hippocampus.
Highlights
Nuclear factor kappa B (NF-κB) is a transcription factor typically expressed with two specific subunits (p50, p65)
Our results show that the absence of the NF-κB p50 subunit decreases late long term potentiation (LTP), but not early phases of LTP and selectively alters long term spatial memory in p50−/−mice
Morris water maze performance in NF-κB p50 Mice In order to assess long term memory in intact animals, we tested p50+/+ and p50−/− mice (n = 6 for each strain) in the MWM, a behavioral paradigm designed for assessing hippocampal-dependent spatial memory
Summary
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. Long term potentiation (LTP), a paradigm used to measure synaptic function and a molecular correlate of memory, along with behavioral tests of memory, are routinely used to assess hippocampal-dependent alterations in synaptic plasticity and memory [11,12,13,14,15,16,17,18,19]. Studies in 2010 by Lehmann et al [23] suggested that p50−/− mice learned more rapidly when attempting to find the hidden platform in the MWM than did wild type mice Given these contradictory findings, questions still remain concerning specific roles for NF-κB in memory especially in a context of the NF-κB p50 subunit
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