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.
Highlights
DF/F correction methods can potentially distort baseline measurements, we rigorously tested and validated three different dF/F methods, and we repeated analyses with raw fluorescence values compared between pairs of sequential trials with different movement times (Figure 2— figure supplement 2; see Methods)
Optogenetic modulation of DANs affected the timing of movements on the concurrent trial, suggesting that DANs can play a “real time” role in behavior. These observations raise two questions of interpretation: 1) what is the mechanistic origin of ramping DAN signals in the self-timed movement task, and 2) how do DAN signals affect self-timed movements in real time? 455 The origin of ramping DAN signals A number of studies have reported short-latency (
The ramping DAN signals we observed during self461 timing were markedly slower, unfolding over seconds and preceding the first-lick by as long as 462 10 s
Summary
18 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. 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. Optogenetic DAN manipulation during the timing interval produced bidirectional changes in the probability of movement timing, with activation causing a bias toward earlier self109 timed movements and suppression causing a bias toward later self-timed movements These combined observations suggest a novel role for the dopaminergic system in the timing of movement initiation, wherein slowly evolving dopaminergic signals, likely driven by reward expectation, can modulate the moment-to-moment probability of whether a reward-related movement will occur
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