Reversible Silencing of Neuronal Excitability in Behaving Mice by a Genetically Targeted, Ivermectin-Gated Cl^− Channel
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 (GluClαβ), 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 GluClαβ-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.
Additional Information
© 2007 Elsevier Inc. Under an Elsevier user license. Received: November 20, 2006; Revised: February 9, 2007; Accepted: February 22, 2007; Published: April 4, 2007. We thank Christof Koch and Herwig Just for helpful discussions, Gabriele Mosconi for laboratory management, Shirley Pease and Janet Baer, D.V.M. for mouse management and assistance with surgical procedures, Dirk Neumann for help with statistics, and Steven Smith for help with the Ethovision Software. D.J.A. is an Investigator of the Howard Hughes Medical Institute. Support for this work was provided by the Moore foundation Conscious Mouse Project and by NIH grant MH-67867 to H.A.L.Attached Files
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Additional details
- Alternative title
- Reversible Silencing of Neuronal Excitability in Behaving Mice by a Genetically Targeted, Ivermectin-Gated Cl− Channel
- Eprint ID
- 55543
- DOI
- 10.1016/j.neuron.2007.02.030
- Resolver ID
- CaltechAUTHORS:20150305-114442340
- Howard Hughes Medical Institute (HHMI)
- Gordon and Betty Moore Foundation
- MH-67867
- NIH
- Created
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2015-03-05Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field