From Molecule to Movement: Dissecting the Path from Dystonia Mutation to Motor Circuit Dysfunction

Abstract

Primary dystonia is a movement disorder remarkable for its selective disruption of motor circuits despite the absence of overt neuropathology. Focusing on DYT1 dystonia, the most common inherited form, this talk will explore how a mutation in the TOR1A gene leads to circuit dysfunction during a defined window of brain development. Studies in genetic models reveal that loss of torsinA function impairs neuronal maturation in ways that are only reversible if corrected early in life, highlighting the existence of a critical period for pathogenesis. This developmental vulnerability helps explain the selectivity of the disease and underscores the importance of timing in potential therapeutic approaches. More broadly, the work illustrates how studying rare genetic diseases can uncover general principles of selective vulnerability, circuit development, and the interplay between pathogenesis and pathophysiology in brain disorders.