CNRS, Centre de Neurosciences Paris-Sud, UMR 8195, Orsay, France; Centre de Neurosciences Paris-Sud, Univ Paris-Sud, UMR 8195, Orsay, France.
Harvard Stem Cell Institute, Harvard Medical School, Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Prog Mol Biol Transl Sci. 2014;122:89-129. doi: 10.1016/B978-0-12-420170-5.00004-0.
The capacity to remember our past experiences and organize our future draws on a number of cognitive processes that allow our brain to form and store neural representations that can be recalled and updated at will. In the brain, these processes require mechanisms of neural plasticity in the activated circuits, brought about by cellular and molecular changes within the neurons activated during learning. At the cellular level, a wealth of experimental data accumulated in recent years provides evidence that signaling from synapses to nucleus and the rapid regulation of the expression of immediate early genes encoding inducible, regulatory transcription factors is a key step in the mechanisms underlying synaptic plasticity and the modification of neural networks required for the laying down of memories. In the activated neurons, these transcriptional events are thought to mediate the activation of selective gene programs and subsequent synthesis of proteins, leading to stable functional and structural remodeling of the activated networks, so that the memory can later be reactivated upon recall. Over the past few decades, novel insights have been gained in identifying key transcriptional regulators that can control the genomic response of synaptically activated neurons. Here, as an example of this approach, we focus on one such activity-dependent transcription factor, Zif268, known to be implicated in neuronal plasticity and memory formation. We summarize current knowledge about the regulation and function of Zif268 in different types of brain plasticity and memory processes.
记忆过去的经历和规划未来的能力依赖于多种认知过程，这些过程使我们的大脑能够形成和存储神经表示，以便可以随意回忆和更新。在大脑中，这些过程需要在激活的电路中具有神经可塑性的机制，这是由学习过程中激活的神经元内的细胞和分子变化引起的。在细胞水平上，近年来积累的大量实验数据提供了证据，表明来自突触到核的信号传递以及编码诱导性调节转录因子的即时早期基因表达的快速调节是突触可塑性机制和神经网络修饰的关键步骤记忆的沉淀。在激活的神经元中，这些转录事件被认为介导了选择性基因程序的激活以及随后的蛋白质合成，导致激活网络的稳定功能和结构重塑，以便可以在回忆时重新激活记忆。在过去的几十年中，人们在确定可以控制突触激活神经元的基因组反应的关键转录调节剂方面取得了新的认识。在这里，作为这种方法的一个例子，我们专注于一种这样的活性依赖性转录因子，即 Zif268，已知其与神经元可塑性和记忆形成有关。我们总结了关于 Zif268 在不同类型的大脑可塑性和记忆过程中的调节和功能的最新知识。
