中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
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《生命科学》 2008, 20(5): 702-
细胞类型特异的遗传学操作:揭开复杂神经环路的面纱
黄佐石
(美国纽约冷泉港实验室)
摘 要:现代神经科学的一个重要课题是阐明复杂神经环路及其细胞组成形成行为的机制。我们希望可以通过对特定神经元群体的区分和操作在引发行为的神经计算和特定神经元群体活性之间建立一种因果联系。运用BAC重组工程技术,我们建立了超过20个“敲入”驱动品系。在这些驱动品系中,Cre或者是可诱导的CreER能够在特定类型的GABA能细胞中表达。另外,我们还建立了一些Cre报告小鼠品系和一个基于病毒转染的蛋白表达系统。这些病毒包含一个Cre-激活的表达元件,可以将一些荧光蛋白或分子开关在体内以很高的效率表达。这种基因操作的策略可以使我们进行如下的一些观察和操作:(1)在突触水平观察中间神经元的形态和他们之间的联系;(2)观察中间神经元的活性及其过往的活动;(3)在生理的时间分辨率上操纵特定细胞群的发放和突触传递。这将使我们对复杂神经环路功能和组织的认识进入一个全新的领域。
关键词:基因学操作;细胞类型特异性启动子;Cre/loxP 重组调节的基因表达; GABA能系统
中图分类号:Q422; Q754  文献标识码:A
 
A cell type-based genetic approach to complex neural circuits
HUANG Z Josh
(Cold Spring Harbor Laboratory, New York, USA)
Abstract: A major challenge in modern neuroscience is to understand how behaviors emerge from the underlying neural networks and their cellular constituents.  To take on this challenge, a productive approach aims to establish causal links between patterns of activity in specific groups of neurons and the computation of neural circuits that guides behavior. Using BAC recombineering (bacterial artificial chromosome engineering) technology, we are generating over 20 knockin "driver lines" expressing Cre or the inducible CreER in specific GABAergic cell types.  In addition, we are constructing a new generation of Cre-activated "reporter" mice and, in particular, Cre-activated viruses to achieve high level expression of fluorescent proteins (FPs) and "molecular switches" (MSs, such as ligand- or light- induced ion channels) in vivo.  These genetic strategies will allow us to: 1) visualize the morphology and connectivity of GABA interneurons with synapse resolution (genetic neuroanatomy); 2) visualize the activity and activity-history of interneurons (genetic neurophysiology); 3) manipulate the firing and synaptic transmission of defined classes of cells at physiological time scales (genetic manipulation).
Key words: genetic access; cell type specific promoters;  Cre/loxP recombination-regulated gene expression; GABAergic system
 
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