biology-1074.pdf (782.91 kB)

Selective inhibition of striatal fast-spiking interneurons causes dyskinesias.

Download (782.91 kB)
journal contribution
posted on 02.11.2011, 00:00 by Aryn Gittis, Daniel K. Leventhal, Benjamin A. Fensterheim, Jeffrey R. Pettibone, Joshua D. Berke, Anatol C. Kreitzer

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

History

Publisher Statement

Copyright © 2011 the authors

Date

02/11/2011

Exports