Pathophysiology of Dyt1 dystonia is mediated by spinal cord dysfunction

Dystonia, a neurological disorder defined by abnormal postures and disorganised movements, is thought to be a neural circuit disorder with dysfunction arising within and between multiple brain regions. Given that spinal circuits are the de facto final common pathway for motor control, we sought to determine their contribution to the movement disorder. We confined a dystonia-related mutation to the spinal cord, which led to behavioural and physiological recapitulation of a severe form of inherited, early-onset, generalised dystonia. These data challenge our current understanding of dystonia, and lead to broader insights into spinal cord function and its involvement in movement disorder pathophysiology. One sentence summary Spinal Tor1a deletion causes severe early onset generalised dystonia, exposing spinal circuitopathy as a key factor in its pathophysiology. ### Competing Interest Statement RMB is a co-founder of Sania Therapeutics, Inc and consults for Sania Rx Ltd.