Cortical pyramidal tract neurons constrain pathological dopaminergic motor responses

Chemogenetic activation of motor cortical pyramidal tract neurons in healthy mice selectively confines pathological dopaminergic motor responses, including reduced axial levodopa-induced dyskinesia.

• Why it matters: The role of pyramidal tract output in parkinsonian and dyskinetic motor states is unclear, limiting circuit-based therapeutic targeting.
• What they did: The authors chemogenetically activated unilateral motor cortical PT neurons in mice, tested effects on spontaneous locomotion, 6-hydroxydopamine lesion deficits, D1-receptor–evoked rotations, and axial levodopa-induced dyskinesia.
• The result: PT stimulation suppressed spontaneous locomotion, did not improve ipsilateral 6-hydroxydopamine lesion motor deficits, attenuated contraversive rotations from D1 stimulation, and reduced axial levodopa dyskinesia by lowering acute D1-mediated c-Fos induction in dopamine-depleted striatum.