神经元活动依赖工具开发应用的研究进展与展望

Research progress and prospect of neural activity-dependent tools

大脑存在数量众多而功能异质的神经元,在响应刺激输入时,特定的神经元类群集结成印迹,构成细胞和环路水平的功能编码单元.为了解析这些功能编码单元,即早基因(IEG)激活、环腺苷酸反应元件结合蛋白(CREB)表达增高及Ca^(2+)内流等细胞活化的特性被相继开发成活动依赖工具,并被大量应用于记忆印迹和事件编码神经集群的解析研究.本文对LacZ-Daun02失活系统、CREB过表达系统、四环素标签工具(TetTag)、活性类群靶向重组工具(TRAP)、活化神经集群捕获工具(CANE)、人工改造的活性启动子工具(E-SARE和RAM)以及光控钙离子依赖工具(Ca-Light和FLARE)等活动依赖工具的原理及应用进行了综述,并展望了活动依赖工具的开发前景.

Despite existing in large numbers with great heterogeneity, neurons form activity clusters in response to specific stimulus inputs.These activity clusters, also called engrams, are functional units that encode information at the cell and circuitry levels. Cell activation generally induces elevated CREB level, IEG expression and Ca2+influx, from which a variety of activity-dependent tools have been developed. These tools are widely used in memory engram and neural ensemble research. In this article, we review the principles and applications of these activity-dependent tools, including Lac Z-Daun02 inactivation system, CREB overexpression system, Tet Tag,TRAP, CANE, two synthetic activity-regulated promoters: E-SARE and RAM, and two calcium-and light-gated tools: Cal-light and FLARE. We also discuss the future development of activity-dependent tools.