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The subthalamic nucleus (STN) controls psychomotor activity and is an efficient therapeutic deep brain stimulation target in Parkinson's disease patients. Despite evidence indicating position-dependent therapeutic effects and distinct functions within the STN, input circuit and cellular profile in the STN remain largely unclear. Using advanced neuroanatomical techniques, we constructed a comprehensive connectivity map of the indirect and hyperdirect pathways in both the mouse and human STN. Our detailed circuit- and cellular-level connectivity revealed a topographically graded organization with three convergent types of indirect and hyperdirect-pathways. Furthermore, we identified two functional types of glutamatergic STN neurons (parvalbumin, PV +/- neurons) segregated with a topographical distribution. Glutamatergic PV+ STN neurons contribute to burst firing. We confirmed synaptic connectivity from indirect and hyperdirect pathways to both PV+ and PV-. These data suggest a complex interplay of information integration within the basal ganglia underlying coordinated movement control and therapeutic effects.

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