NF-kappa B functions in synaptic signaling and behavior.
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.
Meffert
Mollie K
MK
Division of Biology, MC204-31 California Institute of Technology, Pasadena, California 91125, USA.
Chang
Jolene M
JM
Wiltgen
Brian J
BJ
Fanselow
Michael S
MS
Baltimore
David
D
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013570:Synaptic Membranes / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D013574:Synaptosomes; D051996:Transcription Factor RelA; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology
D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D051996:Transcription Factor RelA; D014157:Transcription Factors; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium