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A mouse line for inducible and reversible silencing of specific neurons

机译：可诱导和可逆沉默特定神经元的小鼠系

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Background 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. Results 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. Conclusion This Rosa26-IVMR mouse line provides a powerful tool for exploring selective circuit functions in freely behaving mice.
机译：背景技术用于诱导和可逆地抑制特定神经元神经元活动的遗传方法对于探索神经元回路的功能至关重要。工程化的人类甘氨酸受体被称为伊维菌素（IVM）门控沉默受体（IVMR），在体外具有这种能力。结果在这里我们产生了一条小鼠系，其中IVMR编码序列被插入到loxP侧翼STOP盒下游的ROSA26基因座中。 Cre介导的IVMR特异性表达是通过纹状体中Cre的错误表达以及与多个Cre谱系杂交而揭示的。全身性施用IVM后，在具有单侧纹状体Cre表达的Rosa26-IVMR小鼠中观察到行为改变，当再次使用IVM时，行为改变可以重新开始。在IVM处理的自由移动Rosa26-IVMR; Emx1-Cre小鼠中记录了神经元放电的显着减少，并且通过在脑切片中记录，神经元兴奋性在数分钟内降低。结论该Rosa26-IVMR小鼠品系为探索行为自由的小鼠中的选择性电路功能提供了强大的工具。

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