Striatal circuits support broadly opponent aspects of action suppression and production

Summary

Imbalance between action suppression and production characterizes several basal ganglia (BG) disorders. Relatedly, the direct and indirect pathways of the BG are hypothesized to promote and suppress actions, respectively. Yet striatal direct (dMSNs) and indirect (iMSNs) medium spiny neurons are coactive around movement, apparently contradicting direct-indirect functional opponency. In the dorsolateral striatum of mice, we observed coactivation around movements, but elevated and diminished activity of iMSNs and dMSNs, respectively, during action suppression. Furthermore, relative activity of the two hemispheres evolved in opposite directions in the two pathways as the need to suppress movements to either side of the body developed over time. Lastly, optogenetic inhibition experiments revealed the necessity of iMSNs but not dMSNs for the proactive suppression of specific actions, and dMSNs but not iMSNs for generalized action vigor. These data demonstrate distinct yet still broadly opponent roles for the direct and indirect pathways in behavioral control.