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

4 Citations (Scopus)
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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., ... 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

A mouse line for inducible and reversible silencing of specific neurons. / Hu, Ling; Lan, Wei; Guo, Hao; Chai, Guo-Dong; Huang, Kun; Zhang, Ling; Huang, Ying; Chen, Xue-Feng; Zhang, Lei; Song, Ning-Ning; Chen, Ling; Lang, Bing; Wang, Yun; Wang, Qing-Xiu; Zhang, Jin-Bao; McCaig, Collin; Xu, Lin; Ding, Yu-Qiang.

In: Molecular brain, Vol. 7, 68, 18.09.2014.

Research output: Contribution to journalArticle

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, vol. 7, 68. https://doi.org/10.1186/s13041-014-0068-8
Hu, Ling ; Lan, Wei ; Guo, Hao ; Chai, Guo-Dong ; Huang, Kun ; Zhang, Ling ; Huang, Ying ; Chen, Xue-Feng ; Zhang, Lei ; Song, Ning-Ning ; Chen, Ling ; Lang, Bing ; Wang, Yun ; Wang, Qing-Xiu ; Zhang, Jin-Bao ; McCaig, Collin ; Xu, Lin ; Ding, Yu-Qiang. / A mouse line for inducible and reversible silencing of specific neurons. In: Molecular brain. 2014 ; Vol. 7.
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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.",
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author = "Ling Hu and Wei Lan and Hao Guo and Guo-Dong Chai and Kun Huang and Ling Zhang and Ying Huang and Xue-Feng Chen and Lei Zhang and Ning-Ning Song and Ling Chen and Bing Lang and Yun Wang and Qing-Xiu Wang and Jin-Bao Zhang and Collin McCaig and Lin Xu and Yu-Qiang Ding",
note = "This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements: We thank Dr. Joseph W. Lynch for sharing the IVMR plasmid, and Dr. Lisa M. Monteggia for sharing the AAV2-Cre plasmid. Rosa-CAG targeting vector was obtained from Addgenes. This work was supported by the Key State Research Program from Ministry of Science and Technology of China (2011CB510005, 2012CB966900, 2013CB835103), National Natural Science Foundation of China (81221001, 81200692, 81101026, 31100788, 31271182, 31030034, 91232724), Science and Technology Commission of Shanghai Municipality (12XD1404800), Shanghai Pujiang Program (12PJ1408800), Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (PWZxq2014-04) and Sino-UK Higher Education Research Partnership for PhD Studies.",
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AU - Hu, Ling

AU - Lan, Wei

AU - Guo, Hao

AU - Chai, Guo-Dong

AU - Huang, Kun

AU - Zhang, Ling

AU - Huang, Ying

AU - Chen, Xue-Feng

AU - Zhang, Lei

AU - Song, Ning-Ning

AU - Chen, Ling

AU - Lang, Bing

AU - Wang, Yun

AU - Wang, Qing-Xiu

AU - Zhang, Jin-Bao

AU - McCaig, Collin

AU - Xu, Lin

AU - Ding, Yu-Qiang

N1 - This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements: We thank Dr. Joseph W. Lynch for sharing the IVMR plasmid, and Dr. Lisa M. Monteggia for sharing the AAV2-Cre plasmid. Rosa-CAG targeting vector was obtained from Addgenes. This work was supported by the Key State Research Program from Ministry of Science and Technology of China (2011CB510005, 2012CB966900, 2013CB835103), National Natural Science Foundation of China (81221001, 81200692, 81101026, 31100788, 31271182, 31030034, 91232724), Science and Technology Commission of Shanghai Municipality (12XD1404800), Shanghai Pujiang Program (12PJ1408800), Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (PWZxq2014-04) and Sino-UK Higher Education Research Partnership for PhD Studies.

PY - 2014/9/18

Y1 - 2014/9/18

N2 - 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.

AB - 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.

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KW - Ligand-gated channel

KW - Ivermectin

KW - Rosa26

KW - mammalian neurons

KW - neural circuits

KW - ivermectin

KW - mice

KW - receptor

KW - inactivation

KW - expression

KW - drosphilia

KW - vectors

KW - pathway

U2 - 10.1186/s13041-014-0068-8

DO - 10.1186/s13041-014-0068-8

M3 - Article

VL - 7

JO - Molecular brain

JF - Molecular brain

SN - 1756-6606

M1 - 68

ER -