Reversible silencing of neuronal excitability in behaving mice by a genetically targeted, ivermectin-gated Cl- channel

Neuron. 2007 Apr 5;54(1):35-49. doi: 10.1016/j.neuron.2007.02.030.


Several genetic strategies for inhibiting neuronal function in mice have been described, but no system that directly suppresses membrane excitability and is triggered by a systemically administered drug, has been validated in awake behaving animals. We expressed unilaterally in mouse striatum a modified heteromeric ivermectin (IVM)-gated chloride channel from C. elegans (GluClalphabeta), systemically administered IVM, and then assessed amphetamine-induced rotational behavior. Rotation was observed as early as 4 hr after a single intraperitoneal IVM injection (10 mg/kg), reached maximal levels by 12 hr, and was almost fully reversed by 4 days. Multiple cycles of silencing and recovery could be performed in a single animal. In striatal slice preparations from GluClalphabeta-expressing animals, IVM rapidly suppressed spiking. The two-subunit GluCl/IVM system permits "intersectional" strategies designed to increase the cellular specificity of silencing in transgenic animals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / genetics
  • Amphetamine / pharmacology
  • Animals
  • Antiparasitic Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Chloride Channels* / drug effects
  • Chloride Channels* / genetics
  • Corpus Striatum / cytology
  • Drug Interactions
  • Gene Expression
  • In Vitro Techniques
  • Ion Channel Gating / drug effects*
  • Ion Channel Gating / genetics
  • Ivermectin / pharmacology*
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Motor Activity / drug effects
  • Neural Inhibition / drug effects
  • Neural Inhibition / genetics*
  • Neurons / drug effects*
  • Neurons / physiology
  • Phosphopyruvate Hydratase / metabolism
  • Time Factors


  • Antiparasitic Agents
  • Caenorhabditis elegans Proteins
  • Chloride Channels
  • Luminescent Proteins
  • Ivermectin
  • Amphetamine
  • Phosphopyruvate Hydratase