Selective Inhibition of Striatal Fast-Spiking Interneurons Causes Dyskinesias

摘要: Fast-spiking interneurons (FSIs) can exert powerful control over striatal output, and deficits in this cell population have been observed human patients with Tourette syndrome rodent models of dystonia. However, a direct experimental test FSI involvement motor has never performed. We applied novel pharmacological approach to examine the behavioral consequences selective suppression mouse striatum. IEM-1460, an inhibitor GluA2-lacking AMPARs, selectively blocked synaptic excitation FSIs but not projection neurons. Infusion IEM-1460 into sensorimotor striatum reduced firing rate other populations, elicited robust dystonia-like impairments. These results provide evidence that hypofunction produce movement abnormalities, suggest they may represent therapeutic target for treatment hyperkinetic disorders.