# Cortically Dependent Motor Training Does Not Induce Abnormal Movements in DYT1‐Knock In Mice

## TL;DR

DYT1 dystonia mouse models do not develop abnormal movements when performing a skilled reach task, suggesting cortical training alone may not trigger dystonia.

## Contribution

Demonstrates that cortically-dependent motor training does not induce dystonia-like movements in DYT1-knock in mice.

## Key findings

- DYT1-KI mice performed cortically-dependent reach-to-grasp tasks as well as controls.
- Only subtle abnormal limb shaking occurred in a few trials, not specific to DYT1-KI mice.
- No meaningful abnormal movements were developed in DYT1-KI mice after training.

## Abstract

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.

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.

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.

DYT1‐KI mice learn and perform skilled reach‐to‐grasp comparably to control mice without developing meaningful abnormal movements.

DYT1 dystonia is a familial autosomal dominant, childhood onset dystonia. Mouse models recapitulating the human genotype do not exhibit overtly dystonic movements. It is unclear whether cortically‐dependent tasks are necessary for the development of dystonic movements. DYT1‐KI and control mice perform a cortically‐dependent reach‐to‐grasp task comparably without developing abnormal movements.