A mouse line for inducible and reversible silencing of specific neurons

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• 作者：Ling Hu (1) (2) (3)
  Wei Lan (1) (2) (3)
  Hao Guo (4)
  Guo-Dong Chai (5)
  Kun Huang (5)
  Ling Zhang (1) (2)
  Ying Huang (1) (2)
  Xue-Feng Chen (4)
  Lei Zhang (1) (2)
  Ning-Ning Song (1) (2)
  Ling Chen (1) (2)
  Bing Lang (3)
  Yun Wang (6)
  Qing-Xiu Wang (5)
  Jin-Bao Zhang (7)
  Collin McCaig (3)
  Lin Xu (4)
  Yu-Qiang Ding (1) (2)
  
  1. Key Laboratory of Arrhythmias ; Ministry of Education of China ; East Hospital ; Tongji University School of Medicine ; Shanghai ; 200120 ; China
  2. Department of Anatomy and Neurobiology ; Tongji University School of Medicine ; Shanghai ; 200092 ; China
  3. School of Medical Sciences ; Institute of Medical Sciences ; University of Aberdeen ; Foresterhill ; Aberdeen ; AB25 2ZD ; UK
  4. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province ; Kunming Institute of Zoology ; Kunming ; Yunnan ; 650223 ; China
  5. Department of Anesthesiology ; East Hospital ; Tongji University School of Medicine ; Shanghai ; 200120 ; China
  6. Institutes of Brain Science ; State Key Laboratory for Medical Neurobiology ; Fudan University ; Shanghai ; 200032 ; China
  7. Institute of Neuroscience ; School of Basic Medical Sciences ; Wenzhou Medical University ; Wenzhou ; Zhejiang ; 325035 ; China
  
• 关键词：Neuron silencing ; Ligand ; gated channel ; Ivermectin ; Rosa26
• 刊名：Molecular Brain
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：7
• 期：1
• 全文大小：1,916 KB
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• 刊物主题：Neurosciences; Neurology;
• 出版者：BioMed Central
• ISSN：1756-6606

文摘

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.