Cortically Dependent Motor Training Does Not Induce Abnormal Movements in DYT1-Knock In Mice.

Abstract

PURPOSE: DYT1 dystonia is the most common inherited dystonia, but mouse models recapitulating the human genotype do not exhibit overtly dystonic movements. Because cortical and striatal plasticity are implicated in dystonia pathogenesis, we hypothesized that repetitive performance of a cortically-dependent reach-to-grasp task would induce abnormal dystonia-like movements in DYT1-knock in (DYT-KI) mice. The goal of these experiments was to test that hypothesis. METHODS: TorsinA ΔE (DYT1-KI) mutant mice and non-transgenic littermates (control) were trained to perform a cortically-dependent single pellet reach-to-grasp task using an automated skilled reach-to-grasp apparatus. Task performance and the presence of abnormal movements were manually scored by reviewers blinded to genotype. RESULTS: Six DYT1-KI and five littermate control mice performed at least 500 skilled reaches per animal. There were no differences in success or fumble rate between DYT1-KI and control mice. DYT1-KI mice exhibited subtle abnormal limb shaking in five trials, but a similar movement occurred in one control mouse in one trial. CONCLUSIONS: DYT1-KI mice learn and perform skilled reach-to-grasp comparably to control mice without developing meaningful abnormal movements.