Slowly evolving dopaminergic activity modulates the moment-to-moment probability of movement initiation

ABSTRACT Clues from human movement disorders have long suggested that the neurotransmitter dopamine plays a key role in motor control, but how the endogenous dopaminergic system regulates movement is unknown. Here we show dynamic dopaminergic signaling over seconds-long timescales controls movement timing in mice. Animals were trained to initiate licking after a self-timed interval following a start-timing cue. The movement time was variable from trial-to-trial, as expected from previous studies. Surprisingly, dopaminergic signals ramped-up over seconds between the start-timing cue and the self-timed movement, with variable dynamics that predicted the movement time on single trials. Steeply rising signals preceded early lick-initiation, whereas slowly rising signals preceded later initiation. Higher baseline signals also predicted earlier self-timed movements. Optogenetic activation of dopamine neurons during self-timing did not trigger immediate movements, but rather caused systematic early-shifting of movement initiation, whereas inhibition caused late-shifting, as if modulating the probability of movement. Consistent with this view, the dynamics of the endogenous dopaminergic signals quantitatively predicted the moment-by-moment probability of movement initiation on single trials. These results reveal a causal role for dynamic dopaminergic signaling unfolding over seconds in modulating the decision of when to move.