Abstract
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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials / drug effects
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Action Potentials / genetics
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Amphetamine / pharmacology
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Animals
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Antiparasitic Agents / pharmacology*
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Behavior, Animal / drug effects
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Behavior, Animal / physiology*
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Caenorhabditis elegans
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Caenorhabditis elegans Proteins
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Chloride Channels* / drug effects
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Chloride Channels* / genetics
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Corpus Striatum / cytology
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Drug Interactions
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Gene Expression
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In Vitro Techniques
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Ion Channel Gating / drug effects*
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Ion Channel Gating / genetics
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Ivermectin / pharmacology*
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Luminescent Proteins / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Motor Activity / drug effects
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Neural Inhibition / drug effects
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Neural Inhibition / genetics*
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Neurons / drug effects*
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Neurons / physiology
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Phosphopyruvate Hydratase / metabolism
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Time Factors
Substances
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Antiparasitic Agents
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Caenorhabditis elegans Proteins
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Chloride Channels
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Luminescent Proteins
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Ivermectin
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Amphetamine
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Phosphopyruvate Hydratase