Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations.

Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations.
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DOI:
10.1016/j.neuron.2013.03.025
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发表时间:
2013-06-05
期刊:
影响因子:
16.2
通讯作者:
Luo L
Luo L
中科院分区:
医学1区
文献类型:
--
作者:
Guenthner CJ;Miyamichi K;Yang HH;Heller HC;Luo L

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将用于神经回路解剖的遗传编码工具靶向到相关细胞群体是神经生物学中的主要挑战。我们开发了一种新方法,即活跃群体中的靶向重组(TRAP),以获得对由特定刺激激活的神经元的遗传访问。该方法利用小鼠,其中他莫昔芬依赖性重组酶CreERT2以活性依赖性方式从即刻早期基因Arc和Fos的基因座表达。表达CreERT2的活性细胞只有在他莫昔芬存在时才能进行重组,从而允许遗传进入在不到12小时的时间窗口内活跃的神经元。我们表明,TRAP可以选择性地提供特定的体感,视觉和听觉刺激激活的神经元,并在一个新的环境中的经验。当与标记,跟踪,记录和操纵神经元的工具相结合时,TRAP为理解大脑如何处理信息和产生行为提供了一种强大的新方法。
Targeting genetically encoded tools for neural circuit dissection to relevant cellular populations is a major challenge in neurobiology. We developed a new approach, Targeted Recombination in Active Populations (TRAP), to obtain genetic access to neurons that were activated by defined stimuli. This method utilizes mice in which the tamoxifen-dependent recombinase CreERT2 is expressed in an activity-dependent manner from the loci of the immediate early genes Arc and Fos. Active cells that express CreERT2 can undergo recombination only when tamoxifen is present, allowing genetic access to neurons that are active during a time window of less than 12 h. We show that TRAP can selectively provide access to neurons activated by specific somatosensory, visual, and auditory stimuli, and by experience in a novel environment. When combined with tools for labeling, tracing, recording, and manipulating neurons, TRAP offers a powerful new approach for understanding how the brain processes information and generates behavior.
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