Fig. 5

Efficient pathway and structure unveiled by deep brain stimulation (DBS) with optogenetics and closed-loop control. Selected anatomical connections are illustrated in a simplified cortico–basal ganglia circuitry. Optogenetic selective activation revealed that unlike the indirect pathway, activation of medium spiny neurons expressing the dopamine D1 receptor—i.e. direct pathway—in the striatum [3] and high-frequency stimulations to fibers from cortex layer V to subthalamic nucleus (STH)—i.e. hyperdirect pathway [4]—ameliorate parkinsonism. In addition, closed-loop stimulations to the internal segment of the globus pallidus (GPi), triggered by spiking activity of the motor cortex, are efficient for improving parkinsonism [8]. These reports suggest that the hyperdirect pathway (green lines) alone or together with its downstream structures, including cortex layer V, striatum and STH (green-shaded areas) play a crucial role in DBS treatment. GPe External segment of globus pallidus, GABA gamma-aminobutyric acid