NF-kappa B functions in synaptic signaling and behavior

Mollie K Meffert; Jolene M Chang; Brian J Wiltgen; Michael S Fanselow; David Baltimore

doi:10.1038/nn1110

NF-kappa B functions in synaptic signaling and behavior

Nat Neurosci. 2003 Oct;6(10):1072-8. doi: 10.1038/nn1110. Epub 2003 Aug 31.

Authors

Mollie K Meffert¹, Jolene M Chang, Brian J Wiltgen, Michael S Fanselow, David Baltimore

Affiliation

¹ Division of Biology, MC204-31 California Institute of Technology, Pasadena, California 91125, USA.

PMID: 12947408
DOI: 10.1038/nn1110

Abstract

Ca(2+)-regulated gene transcription is essential to diverse physiological processes, including the adaptive plasticity associated with learning. We found that basal synaptic input activates the NF-kappa B transcription factor by a pathway requiring the Ca(2+)/calmodulin-dependent kinase CaMKII and local submembranous Ca(2+) elevation. The p65:p50 NF-kappa B form is selectively localized at synapses; p65-deficient mice have no detectable synaptic NF-kappa B. Activated NF-kappa B moves to the nucleus and could directly transmute synaptic signals into altered gene expression. Mice lacking p65 show a selective learning deficit in the spatial version of the radial arm maze. These observations suggest that long-term changes to adult neuronal function caused by synaptic stimulation can be regulated by NF-kappa B nuclear translocation and gene activation.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Active Transport, Cell Nucleus / genetics
Animals
Animals, Newborn
Behavior, Animal / physiology*
Calcium / metabolism
Calcium Signaling / genetics
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
Cells, Cultured
Hippocampus / cytology
Hippocampus / drug effects
Hippocampus / metabolism
Mice
NF-kappa B / genetics
NF-kappa B / metabolism*
Neurons / drug effects
Neurons / metabolism*
Recombinant Fusion Proteins / pharmacology
Signal Transduction / genetics
Synapses / drug effects
Synapses / metabolism*
Synaptic Membranes / genetics
Synaptic Membranes / metabolism
Synaptic Transmission / drug effects
Synaptic Transmission / genetics*
Synaptosomes
Transcription Factor RelA
Transcription Factors / deficiency
Transcription Factors / genetics
Transcription, Genetic / physiology

Substances

NF-kappa B
Recombinant Fusion Proteins
Transcription Factor RelA
Transcription Factors
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Calcium