Roles for NF-κB and gene targets of NF-κB in synaptic plasticity, memory, and navigation

Mol Neurobiol. 2014 Apr;49(2):757-70. doi: 10.1007/s12035-013-8555-y. Epub 2013 Oct 13.


Although traditionally associated with immune function, the transcription factor nuclear factor kappa B (NF-κB) has garnered much attention in recent years as an important regulator of memory. Specifically, research has found that NF-κB, localized in both neurons and glia, is activated during the induction of long-term potentiation (LTP), a paradigm of synaptic plasticity and correlate of memory. Further, experimental manipulation of NF-κB activation or its blockade results in altered memory and spatial navigation abilities. Genetic knockout of specific NF-κB subunits in mice results in memory alterations. Collectively, such data suggest that NF-κB may be a requirement for memory, although the direction of the response (i.e., memory enhancement or deficit) is inconsistent. A limited number of gene targets of NF-κB have been recently identified in neurons, including neurotrophic factors, calcium-regulating proteins, other transcription factors, and molecules associated with neuronal outgrowth and remodeling. In turn, several key molecules are activators of NF-κB, including protein kinase C and [Ca(++)]i. Thus, NF-κB signaling is complex and under the regulation of numerous proteins involved in activity-dependent synaptic plasticity. The purpose of this review is to highlight the literature detailing a role for NF-κB in synaptic plasticity, memory, and spatial navigation. Secondly, this review will synthesize the research evaluating gene targets of NF-κB in synaptic plasticity and memory. Although there is ample evidence to suggest a critical role for NF-κB in memory, our understanding of its gene targets in neurons is limited and only beginning to be appreciated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Targeting / methods*
  • Humans
  • Long-Term Potentiation / physiology
  • Memory / physiology*
  • Mice
  • NF-kappa B / physiology*
  • Neuronal Plasticity / physiology*
  • Spatial Behavior / physiology*
  • Synapses / physiology*


  • NF-kappa B