کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4322668 | 1291723 | 2007 | 15 صفحه PDF | دانلود رایگان |
SummarySeveral 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.
Journal: - Volume 54, Issue 1, 5 April 2007, Pages 35–49