A mouse line for inducible and reversible silencing of specific neurons.

A mouse line for inducible and reversible silencing of specific neurons.
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用于特定神经元可诱导和可逆沉默的小鼠品系

DOI:
10.1186/s13041-014-0068-8
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发表时间:
2014-09-18
期刊:
影响因子:
3.6
通讯作者:
Ding YQ
Ding YQ
中科院分区:
医学3区
文献类型:
--
作者:
Hu L;Lan W;Guo H;Chai GD;Huang K;Zhang L;Huang Y;Chen XF;Zhang L;Song NN;Chen L;Lang B;Wang Y;Wang QX;Zhang JB;McCaig C;Xu L;Ding YQ

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遗传方法可诱导和可逆地抑制特定神经元的神经元活动,对于探索神经元回路的功能至关重要。体外实验表明,被称为伊维菌素(IVM)门控沉默受体(IVMR)的工程化人甘氨酸受体具有这种能力。在这里,我们产生了一个小鼠系,其中IVMR编码序列被插入到loxP侧翼停止盒下游的rosa26基因座中。Cre在纹状体中的错误表达以及与几个Cre系的杂交表明了Cre介导的IVMR的特异性表达。单侧纹状体Cre表达的ROSA26-IVMR小鼠全身注射IVM后可观察到行为学改变,再次应用IVM后可重新启动。在IVM处理的自由活动Rosa26-IVMR;Emx1-Cre小鼠中,神经元放电显著减少,脑片记录显示,神经元的兴奋性在几分钟内降低。这一rosa26-IVMR小鼠品系为探索自由行为小鼠的选择性电路功能提供了一个强大的工具。本文的在线版本(doi:10.1186/s13041-0140068-8)包含补充材料,授权用户可以使用。
Genetic methods for inducibly and reversibly inhibiting neuronal activity of specific neurons are critical for exploring the functions of neuronal circuits. The engineered human glycine receptor, called ivermectin (IVM)-gated silencing receptor (IVMR), has been shown to possess this ability in vitro. Here we generated a mouse line, in which the IVMR coding sequence was inserted into the ROSA26 locus downstream of a loxP-flanked STOP cassette. Specific Cre-mediated IVMR expression was revealed by mis-expression of Cre in the striatum and by crossing with several Cre lines. Behavioral alteration was observed in Rosa26-IVMR mice with unilateral striatal Cre expression after systemic administration of IVM, and it could be re-initiated when IVM was applied again. A dramatic reduction in neuron firing was recorded in IVM-treated free moving Rosa26-IVMR;Emx1-Cre mice, and neuronal excitability was reduced within minutes as shown by recording in brain slice. This Rosa26-IVMR mouse line provides a powerful tool for exploring selective circuit functions in freely behaving mice. The online version of this article (doi:10.1186/s13041-014-0068-8) contains supplementary material, which is available to authorized users.
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