"Selective inhibition of striatal fast-spiking interneurons elicits dystonia"

Abstract

Fast-spiking interneurons (FSIs) can exert powerful control over striatal output, and deficits in this cell population have been observed inhuman patients with Tourette syndrome and rodent models of dystonia. However, a direct experimental test of striatal FSI involvementin motor control has never been performed. We applied a novel pharmacological approach to examine the behavioral consequences ofselective FSI suppression in mouse striatum. IEM-1460, an inhibitor of GluA2-lacking AMPARs, selectively blocked synaptic excitation ofFSIs but not striatal projection neurons. Infusion of IEM-1460 into the sensorimotor striatum reduced the firing rate of FSIs but not othercell populations, and elicited robust dystonia-like impairments. These results provide direct evidence that hypofunction of striatal FSIscan produce movement abnormalities, and suggest that they may represent a novel therapeutic target for the treatment of hyperkineticmovement disorders. © 2011 the authors.