期刊
NEURON
卷 54, 期 1, 页码 35-49出版社
CELL PRESS
DOI: 10.1016/j.neuron.2007.02.030
关键词
-
资金
- NIMH NIH HHS [MH-67867] Funding Source: Medline
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 (GluCl alpha beta), 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 GluCl alpha beta-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.
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