Nedivi E, Hevroni D, Naot D, Israeli D, Citri Y
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
Nature. 1993 Jun 24;363(6431):718-22. doi: 10.1038/363718a0.
Plasticity is a property of the nervous system that allows it to modify its response to an altered input. This capacity for change suggests that there are molecular mechanisms in neurons that can couple stimuli to long-term alterations in phenotype. Neuronal excitation elicits rapid transcriptional activation of several immediate-early genes, for example c-fos, c-jun and zif268. Many immediate-early genes encode transcription factors that control expression of downstream genes whose products are believed to bring about long-term plastic changes. Here we use a highly sensitive differential complementary DNA cloning procedure to identify genes that may participate in long-term plasticity. We cloned 52 cDNAs of genes induced by the glutamate analogue kainate in the hippocampus dentate gyrus. The number of these candidate plasticity-related genes (CPGs) is estimated to be 500-1,000. One of the cloned CPGs (16C8), encoding a protease inhibitor, is induced by a stimulus producing long-term potentiation and during dentate gyrus development; a second, cpg1, is dependent on activation of the NMDA (N-methyl-D-aspartate) receptor for induction and encodes a new small, dentate-gyrus-specific protein. Seventeen of the cloned CPGs encode known proteins, including six suggesting that strong neuronal activation leads to de novo synthesis of vesicular and other synaptic components.
可塑性是神经系统的一种特性，使其能够改变对改变后的输入的反应。这种变化能力表明，神经元中存在分子机制，可将刺激与表型的长期改变联系起来。神经元兴奋会引发几个立即早期基因（如c-fos、c-jun和zif268）的快速转录激活。许多立即早期基因编码转录因子，这些转录因子控制下游基因的表达，其产物被认为会导致长期的可塑性变化。在这里，我们使用一种高度敏感的差异互补DNA克隆程序来鉴定可能参与长期可塑性的基因。我们克隆了海马齿状回中由谷氨酸类似物海人酸诱导的52个基因的cDNA。这些候选可塑性相关基因（CPG）的数量估计为500-1000个。其中一个克隆的CPG（16C8）编码一种蛋白酶抑制剂，它在产生长期增强作用的刺激下以及在齿状回发育过程中被诱导；另一个是cpg1，其诱导依赖于NMDA（N-甲基-D-天冬氨酸）受体的激活，并且编码一种新的、小的、齿状回特异性蛋白。17个克隆的CPG编码已知蛋白质，其中6个表明强烈的神经元激活会导致囊泡和其他突触成分的从头合成。
