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-κB transcription factor by a pathway requiring the Ca 2+/calmodulin-dependent kinase CAMKII and local submembranous Ca 2+ elevation. The p65:p50 NF-κB form is selectively localized at synapses; p65-deficient mice have no detectable synaptic NF-κB. Activated NF-κB 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-κB nuclear translocation and gene activation.
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