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

Lerchner, Walter and Xiao, Cheng and Nashmi, Raad and Slimko, Eric M. and van Trigt, Laurent and Lester, Henry A. and Anderson, David J. (2007) Reversible Silencing of Neuronal Excitability in Behaving Mice by a Genetically Targeted, Ivermectin-Gated Cl^− Channel. Neuron, 54 (1). pp. 35-49. ISSN 0896-6273. https://resolver.caltech.edu/CaltechAUTHORS:20150305-114442340

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.neuron.2007.02.030DOIArticle
ORCID:
AuthorORCID
Xiao, Cheng0000-0001-9649-7450
Lester, Henry A.0000-0002-5470-5255
Anderson, David J.0000-0001-6175-3872
Alternate Title:Reversible Silencing of Neuronal Excitability in Behaving Mice by a Genetically Targeted, Ivermectin-Gated Cl− Channel
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.
Funders:
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Gordon and Betty Moore FoundationUNSPECIFIED
NIHMH-67867
Issue or Number:1
Record Number:CaltechAUTHORS:20150305-114442340
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150305-114442340
Official Citation:Lerchner, W., Xiao, C., Nashmi, R., Slimko, E. M., van Trigt, L., Lester, H. A., & Anderson, David J. (2007). Reversible Silencing of Neuronal Excitability in Behaving Mice by a Genetically Targeted, Ivermectin-Gated Cl− Channel. Neuron, 54(1), 35-49. doi: http://dx.doi.org/10.1016/j.neuron.2007.02.030
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:55543
Collection:CaltechAUTHORS
Deposited By: Joanne McCole
Deposited On:05 Mar 2015 20:11
Last Modified:27 Mar 2020 21:41

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