Action-specific ensembles of both D1- and D2-medium spiny neurons in the dorsolateral striatum equally encode the identity of granular forelimb actions distinguished by distinct muscle activation patterns, and closed-loop optogenetic stimulation of these ensembles causally increases force production selectively for the congruent action, establishing that striatal ensembles control specific ongoing actions rather than providing general motor invigoration.

The ability of the brain to control specific fine actions is crucial for survival. Although striatal dysfunction underlies numerous movement disorders, its activity has classically been studied in the context of movement reinforcement and invigoration. Recent studies have revealed that striatal activity encodes specific whole-body and forelimb movements. However, it is unclear if this activity actually controls specific movements. We developed a closed-loop system to identify and manipulate action-specific neuronal ensembles in real time using holographic optogenetics through a GRIN lens. We designed an isometric force task in which mice performed push or pull actions on an immobile joystick without overt kinematics—actions that engage the same forelimb muscles but with different activation patterns. Using 2-photon calcium imaging, we simultaneously recorded D1- and D2-medium spiny neurons (MSNs) in the dorsolateral striatum - classically viewed as promoting versus inhibiting movement – and found that both populations equally encoded isometric action identity. Stimulation of action-specific D1- and D2-MSN ensembles increased ongoing force, but only when the stimulated ensemble was congruent with the ongoing action. These results reveal that specific ensembles of D1- and D2-MSNs control specific actions, as granular as distinct muscle activation patterns of the same forelimb. These findings provide a novel framework for understanding how striatal dysfunction can produce highly specific movement impairments in Huntington’s disease and dystonia.