Genetic Approaches to Investigate the Role of CREB in Neuronal Plasticity and Memory
Genetic Approaches to Investigate the Role of CREB in Neuronal Plasticity and Memory
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DOI：
10.1007/s12035-011-8209-x
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发表时间：
2011-12-01
影响因子：
5.1
通讯作者：
Marie, Helene
中科院分区：
文献类型：
--
作者：
Barco, Angel;Marie, Helene
在神经元中，导致cAMP反应元件结合蛋白（CREB）激活的多个细胞内信号级联的会聚表明，这种转录因子在整合不同的输入和介导适当的神经元反应中起着关键作用。这种转录反应的性质取决于刺激的类型和强度以及细胞环境。CREB依赖性基因表达涉及神经系统功能的许多不同方面，从胚胎发育到神经元存活，以及突触、结构和内在可塑性。在这里，我们首先回顾了不同的方法学方法用于遗传操纵CREB活性和水平在体内的神经元在成人大脑中，包括重组病毒载体，小鼠转基因，和基因靶向技术。然后，我们讨论了这些方法对我们理解CREB在啮齿动物神经元可塑性和记忆中的作用的影响。将这些遗传学方法与电生理学和行为学相结合的研究提供了强有力的证据，证明CREB在突触可塑性、内在兴奋性和长期记忆形成的调节中起着重要作用。这些发现为开发治疗记忆障碍的新治疗策略铺平了道路。
In neurons, the convergence of multiple intracellular signaling cascades leading to cAMP-responsive element-binding protein (CREB) activation suggests that this transcription factor plays a critical role in integrating different inputs and mediating appropriate neuronal responses. The nature of this transcriptional response depends on both the type and strength of the stimulus and the cellular context. CREB-dependent gene expression has been involved in many different aspects of nervous system function, from embryonic development to neuronal survival, and synaptic, structural, and intrinsic plasticity. Here, we first review the different methodological approaches used to genetically manipulate CREB activity and levels in neurons in vivo in the adult brain, including recombinant viral vectors, mouse transgenesis, and gene-targeting techniques. We then discuss the impact of these approaches on our understanding of CREB's roles in neuronal plasticity and memory in rodents. Studies combining these genetic approaches with electrophysiology and behavior provide strong evidence that CREB is critically involved in the regulation of synaptic plasticity, intrinsic excitability, and long-term memory formation. These findings pave the way for the development of novel therapeutic strategies to treat memory disorders.