Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published April 5, 2007 | Supplemental Material
Journal Article Open

Reversible Silencing of Neuronal Excitability in Behaving Mice by a Genetically Targeted, Ivermectin-Gated Cl^− Channel


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

Supplemental Material - mmc1.pdf

Supplemental Material - mmc2.mpeg


Files (37.6 MB)
Name Size Download all
37.5 MB Download
112.8 kB Preview Download

Additional details

August 19, 2023
October 20, 2023