NF-κB functions in synaptic signaling and behavior

Ca2+-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-kappaB transcription factor by a pathway requiring the Ca2+ /calmodulin-dependent kinase CaMKII and local submembranous Ca2+ elevation. The p65: p50 NF-kappaB form is selectively localized at synapses; p65-deficient mice have no detectable synaptic NF-kappaB. Activated NF-kappaB 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-kappaB nuclear translocation and gene activation.