Abstract
Imbalance between action suppression and production characterizes several neurological disorders of the basal ganglia (BG)1. Relatedly, two major circuits of the BG, the direct and indirect pathways, are hypothesized to function in opposition, promoting and suppressing actions, respectively2. Yet activity of neurons initiating the two pathways, striatal direct (dMSNs) and indirect (iMSNs) medium spiny neurons, appears to be positively correlated around movement, apparently contradicting direct-indirect functional opponency3. Here we show that while coactivation occurs during movement, action suppression produces systematic features of functional opponency between the two pathways. First, suppression produced elevated iMSN activity and diminished dMSN activity in dorsolateral striatum of mice. Second, as the need to suppress movements to one or the other side of the body evolved over time, so too did the relative levels of activity in the two hemispheres, and in opposite patterns in the two pathways. Lastly, optogenetic inhibition of dMSNs, but not iMSNs, slowed movements without affecting their likelihood, whereas inhibition of iMSNs, but not dMSNs, disrupted whether and when mice suppressed or produced particular actions. These data demonstrate large-scale opponency in the activity of neurons that initiate the direct and indirect pathways of the BG, but suggest distinct action-related functions of each pathway. Specifically, the data support a novel model of sensorimotor striatum wherein the direct pathway appears to be necessary for augmenting generalized movement vigor, and the indirect pathway for the proactive suppression of specific behaviors.
Competing Interest Statement
The authors have declared no competing interest.