NF-κB/Rel regulates inhibitory and excitatory neuronal function and synaptic plasticity

Alison O'Mahony, Jacob Raber, Mauricio Montano, Erik Foehr, Victor Han, Shao Ming Lu, Hakju Kwon, Anthony LeFevour, Shikha Chakraborty-Sett, Warner C. Greene

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Changes in synaptic plasticity required for memory formation are dynamically regulated through opposing excitatory and inhibitory neurotransmissions. To explore the potential contribution of NF-κB/Rel to these processes, we generated transgenic mice conditionally expressing a potent NF-κB/Rel inhibitor termed IκBα superrepressor (IκBα-SR). Using the prion promoter-enhancer, IκBα-SR is robustly expressed in inhibitory GABAergic interneurons and, at lower levels, in excitatory neurons but not in glia. This neuronal pattern of IκBα-SR expression leads to decreased expression of glutamate decarboxylase 65 (GAD65), the enzyme required for synthesis of the major inhibitory neurotransmitter, γ-aminobutyric acid (GABA) in GABAergic interneurons. IκBα-SR expression also results in diminished basal GluR1 levels and impaired synaptic strength (input/output function), both of which are fully restored following activity-based task learning. Consistent with diminished GAD65-derived inhibitory tone and enhanced excitatory firing, IκBα-SR+ mice exhibit increased late-phase long-term potentiation, hyperactivity, seizures, increased exploratory activity, and enhanced spatial learning and memory. IκBα-SR+ neurons also express higher levels of the activity-regulated, cytoskeleton-associated (Arc) protein, consistent with neuronal hyperexcitability. These findings suggest that NF-κB/Rel transcription factors act as pivotal regulators of activity-dependent inhibitory and excitatory neuronal function regulating synaptic plasticity and memory.

Original languageEnglish (US)
Pages (from-to)7283-7298
Number of pages16
JournalMolecular and cellular biology
Volume26
Issue number19
DOIs
StatePublished - Oct 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    O'Mahony, A., Raber, J., Montano, M., Foehr, E., Han, V., Lu, S. M., Kwon, H., LeFevour, A., Chakraborty-Sett, S., & Greene, W. C. (2006). NF-κB/Rel regulates inhibitory and excitatory neuronal function and synaptic plasticity. Molecular and cellular biology, 26(19), 7283-7298. https://doi.org/10.1128/MCB.00510-06