Fig. 1.

Model of motor control by the nigrostriatal circuit. DA neurons (blue) originating in the substantia nigra project to the striatum, where they release DA onto D₁R- and D₂R-containing GABAergic (red) medium spiny neurons and D₂R-containing cholinergic interneurons (orange). DA, through its interaction with the Gα_s-coupled D₁R, promotes neuronal signaling. In contrast, D₂R-Gα_i/o activation ultimately inhibits neuronal signaling. DA release in the striatum silences GABAergic neurons of the globus pallidus (GP) by enhancing the activity of D₁R-containing GABAergic medium spiny neurons (MSNs) of the direct pathway, increasing GABA release into the GP, and by silencing D₂R-containing GABAergic MSNs that begin the indirect pathway, ultimately decreasing glutamate release into the GP. Silencing of GP GABAergic neurons promotes thalamic glutamatergic (green) signaling to the cortex and proper motor control. Solid axons denote pathways that are “on” and dashed axons represent pathways that are “silent.”