Striatum, critical in DYTI
DYT1 dystonia is an autosomal dominant dystonia that is due to mutations in the TOR1A gene. Current evidence points toward a central role of the striatum (the caudate + putamen complex) in the pathophysiology of DYT1 dystonia. It is not clear, though, how an alteration at the level of striatum can cause widespread network changes (cortical, subcortical, and cerebellar networks). Dr. Vaillancourt’s team recently published evidence that striatal abnormality in a mouse model of DYT1 dystonia “engages genetically normal hindbrain regions into an aberrant connectivity network”. The animal model used is a conditional knockout of torsinA in the mouse’s forebrain affecting cholinergic and GABAergic neurons. Diffusion MRI studies (good marker of microstructural deficits) identified striatum-limited increased free-water corrected tissue mean diffusivity indicating microstructural abnormalities limited to the striatum. This “abnormal” striatum had widespread increased brain connectivity.