Slowly evolving dopaminergic activity modulates the moment-to-moment probability of reward-related self-timed movements

Elife. 2021 Dec 23:10:e62583. doi: 10.7554/eLife.62583.

Abstract

Clues from human movement disorders have long suggested that the neurotransmitter dopamine plays a role in motor control, but how the endogenous dopaminergic system influences movement is unknown. Here, we examined the relationship between dopaminergic signaling and the timing of reward-related movements in mice. Animals were trained to initiate licking after a self-timed interval following a start-timing cue; reward was delivered in response to movements initiated after a criterion time. 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/reward 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. We propose that ramping dopaminergic signals, likely encoding dynamic reward expectation, can modulate the decision of when to move.

Keywords: basal ganglia; behavior; dopamine; mouse; movement initiation; neuroscience; reward; timing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cues
  • Dopamine / metabolism*
  • Dopaminergic Neurons / metabolism
  • Female
  • Humans
  • Male
  • Mice
  • Motor Activity*
  • Movement
  • Movement Disorders / metabolism*
  • Probability
  • Reward*
  • Time Factors

Substances

  • Dopamine