Intralaminar thalamus relays basal ganglia output to the insular cortex to drive tic generation.

Motor and vocal tics accompanied by premonitory urges are hallmark symptoms of Tourette syndrome (TS), yet the underlying neuronal mechanisms remain incompletely understood. Here, we establish a mouse model of tic-like movements by unilateral striatal injection of a GABAA receptor antagonist. This model induces c-Fos activation in both motor and limbic structures, including the insular cortex (IC). Fiber photometry reveals tic-associated activity in IC as well as the primary motor cortex (M1). Viral tracing demonstrates that basal ganglia outputs from the substantia nigra pars reticulata are transmitted to IC via the intralaminar thalamic nuclei (ITN). Chemogenetic inhibition of IC or the thalamo-insular pathway suppresses tic-like behaviors and reduces tic-associated cortical activity. These findings identify IC as a candidate node involved in tic generation and highlight ITN as relay stations linking motor and limbic circuits. Aberrant thalamo-insular signaling may contribute to tic-related pathophysiology and represents a potential circuit-level therapeutic target.