Meffert Mollie K, Chang Jolene M, Wiltgen Brian J, Fanselow Michael S, Baltimore David
Division of Biology, MC204-31 California Institute of Technology, Pasadena, California 91125, USA.
Nat Neurosci. 2003 Oct;6(10):1072-8. doi: 10.1038/nn1110. Epub 2003 Aug 31.
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.
钙（Ca2+）调节的基因转录对于多种生理过程至关重要，包括与学习相关的适应性可塑性。我们发现基础突触输入通过一条需要钙（Ca2+）/钙调蛋白依赖性激酶CaMKII和局部膜下钙（Ca2+）升高的途径激活NF-κB转录因子。p65:p50 NF-κB形式选择性地定位于突触；p65缺陷小鼠没有可检测到的突触NF-κB。激活的NF-κB转移到细胞核，并可直接将突触信号转化为基因表达的改变。缺乏p65的小鼠在放射状臂迷宫的空间版本中表现出选择性学习缺陷。这些观察结果表明，突触刺激引起的成年神经元功能的长期变化可由NF-κB核转位和基因激活来调节。
