Memory consolidation requires activation of a gene expression program that allows de novo protein synthesis. But the molecular mechanisms that favour or restrict that program are poorly understood. The kinase c-Abl can modulate gene expression through transcription factors and chromatin modifiers. Here, we show that c-Abl ablation in the brain improves learning acquisition and memory consolidation in mice. Its absence also affects gene expression profiles in the mouse hippocampus. We found that genes involved in synaptic plasticity and actin cytoskeleton dynamics, such as Arp2 and Thorase, are up-regulated at the mRNA and protein levels in trained c-Abl KO mice and by a chemical-LTP stimulus. Trained c-Abl KO mice also show that dendritic spines are larger than in wild-type mice and present at a higher density. These results indicate that c-Abl kinase is an important part of the mechanism that limits or restricts signalling of relevant gene programs involved in morphological and functional spine changes upon neuronal stimulation.

记忆巩固需要激活允许从头开始的基因表达程序蛋白质合成。但是，人们对支持或限制该程序的分子机制知之甚少。激酶 c-Abl 可以通过转录因子和染色质修饰剂调节基因表达。在这里，我们展示了大脑中的 c-Abl 消融改善了小鼠的学习获取和记忆巩固。它的缺失也会影响小鼠海马中的基因表达谱。我们发现，参与突触可塑性和肌动蛋白细胞骨架动力学的基因，如 Arp2 和 Thorase，在受过训练的 c-Abl KO 小鼠和化学 LTP 刺激下在 mRNA 和蛋白质水平上被上调。受过训练的 c-Abl KO 小鼠还表明，树突棘比野生型小鼠大，并且以更高的密度存在。