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Striatal dysfunction plays an important role in dystonia, but the striatal cell types that contribute to abnormal movements are poorly defined. We demonstrate that conditional deletion of the DYT1 dystonia protein torsinA in embryonic progenitors of forebrain cholinergic and GABAergic neurons causes dystonic-like twisting movements that emerge during juvenile CNS maturation. The onset of these movements coincides with selective degeneration of dorsal striatal large cholinergic interneurons (LCI), and surviving LCI exhibit morphological, electrophysiological, and connectivity abnormalities. Consistent with the importance of this LCI pathology, murine dystonic-like movements are reduced significantly with an antimuscarinic agent used clinically, and we identify cholinergic abnormalities in postmortem striatal tissue from DYT1 dystonia patients. These findings demonstrate that dorsal LCI have a unique requirement for torsinA function during striatal maturation, and link abnormalities of these cells to dystonic-like movements in an overtly symptomatic animal model. DOI: http://dx.doi.org/10.7554/eLife.08352.001, eLife digest Dystonia is disorder of the nervous system that causes people to suffer from abnormal and involuntary twisting movements. These movements are triggered, in part, by irregularities in a part of the brain called the striatum. The most common view among researchers is that dystonia is caused by abnormal activity in an otherwise structurally normal nervous system. But, recent findings indicate that the degeneration of small populations of nerve cells in the brain may be important. The striatum is made up of several different types of nerve cells, but it is poorly understood which of these are affected in dystonia. One type of dystonia, which most often occurs in children, is caused by a defect in a protein called torsinA. Pappas et al. have now discovered that deleting the gene for torsinA from particular populations of nerve cells in the brains of mice (including a population in the striatum) causes abnormal twisting movements. Like people with dystonia, these mice developed the abnormal movements as juveniles, and the movements were suppressed with ‘anti-cholinergic’ medications. Pappas et al. then analyzed brain tissue from these mice and revealed that the twisting movements began at the same time that a single type of cell in the striatum—called ‘cholinergic interneurons’—degenerated. Postmortem studies of brain tissue from dystonia patients also revealed abnormalities of these neurons. Together these findings challenge the notion that dystonia occurs in a structurally normal nervous system and reveal that cholinergic interneurons in the striatum specifically require torsinA to survive. Following on from this work, the next challenges are to identify what causes the selective loss of cholinergic interneurons, and to investigate how this cell loss affects the activity within the striatum. DOI: http://dx.doi.org/10.7554/eLife.08352.002