A mechanism linking dopamine's roles in reinforcement, movement and motivation.

Dopamine neurons (DANs) play seemingly distinct roles in reinforcement, ^1-3 motivation, ^4,5 and movement, ^6,7 and DA-modulating therapies relieve symptoms across a puzzling spectrum of neurologic and psychiatric symptoms. ⁸ Yet, the mechanistic relationship among these roles is unknown. Here, we show DA's tripartite roles are causally linked by a process in which phasic striatal DA rapidly and persistently recalibrates the propensity to move, a measure of vigor. Using a self-timed movement task, we found that single exposures to reward-related DA transients (both endogenous and exogenously-induced) exerted one-shot updates to movement timing-but in a surprising fashion. Rather than reinforce specific movement times, DA transients quantitatively changed movement timing on the next trial, with larger transients leading to earlier movements (and smaller to later), consistent with a stochastic search process that calibrates the frequency of movement. Both abrupt and gradual changes in external and internal contingencies-such as timing criterion, reward content, and satiety state-caused changes to the amplitude of DA transients that causally altered movement timing. The rapidity and bidirectionality of the one-shot effects are difficult to reconcile with gradual synaptic plasticity, and instead point to more flexible cellular mechanisms, such as DA-dependent modulation of neuronal excitability. Our findings shed light on how natural reinforcement, as well as DA-related disorders such as Parkinson's disease, could affect behavioral vigor.