A mouse line for inducible and reversible silencing of specific neurons

Ling Hu, Wei Lan, Hao Guo, Guo-Dong Chai, Kun Huang, Ling Zhang, Ying Huang, Xue-Feng Chen, Lei Zhang, Ning-Ning Song, Ling Chen, Bing Lang, Yun Wang, Qing-Xiu Wang, Jin-Bao Zhang, Collin McCaig, Lin Xu*, Yu-Qiang Ding

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number68
Number of pages10
JournalMolecular brain
Volume7
DOIs
Publication statusPublished - 18 Sep 2014

Keywords

  • Neuron silencing
  • Ligand-gated channel
  • Ivermectin
  • Rosa26
  • mammalian neurons
  • neural circuits
  • ivermectin
  • mice
  • receptor
  • inactivation
  • expression
  • drosphilia
  • vectors
  • pathway

Cite this

Hu, L., Lan, W., Guo, H., Chai, G-D., Huang, K., Zhang, L., Huang, Y., Chen, X-F., Zhang, L., Song, N-N., Chen, L., Lang, B., Wang, Y., Wang, Q-X., Zhang, J-B., McCaig, C., Xu, L., & Ding, Y-Q. (2014). A mouse line for inducible and reversible silencing of specific neurons. Molecular brain, 7, [68]. https://doi.org/10.1186/s13041-014-0068-8