Thalamo-insular pathway regulates tic generation via motor-limbic crosstalk

Tic disorders accompanied by premonitory urges are hallmark symptoms of Tourette syndrome (TS), but the neuronal mechanism remains elusive. Here, we show that striatal disinhibition induces motor tics in mice. This model exhibits c-Fos activation in both motor and limbic structures, such as the insular cortex (IC). Viral tracing demonstrates that aberrant striatal activity is ultimately transmitted to the insular cortex via the intralaminar thalamic nuclei, a potential target of deep brain stimulation in TS patients. We further identify tic-associated activity in the IC as well as the primary motor cortex (M1). Chemogenetic inhibition of the thalamo-insular pathway suppresses synchronous activity in M1, and alleviates tic-like behaviors. These findings reveal motor-limbic circuit dysfunction as a key mechanism underlying tic disorders.