Summary
Deciding when to move is a universal aspect of behavior. Pharmacological studies implicate the neurotransmitter dopamine as a regulator of self-timed movements, with increased dopamine availability generally leading to earlier movements, as if speeding an internal clock. How dopamine affects self-timed movements is unclear; a recent study even suggested that increased activity in nigrostriatal dopamine neurons (DANs) is associated with slower internal timing1. Here we show the dynamics of DAN activity control the timing of self-timed movements in mice. Animals were trained to make a self-timed lick several seconds after a start-timing cue. Movement times were highly variable from trial-to-trial, typical for self-timed actions2–6. Higher pre-trial DAN signals predicted earlier movements, consistent with pharmacological studies. However, surprisingly, DAN signals ramped-up over seconds following the start-timing cue, with the steepness of ramping predicting the trial-by-trial movement time. Steeply ramping signals preceded early lick-times whereas shallow ramping preceded later lick-times, reminiscent of a ramp-to-threshold process. Optogenetic DAN activation during the timed interval caused systematic early-shifting of self-timed movements, whereas inhibition caused systematic late-shifting. These results reveal a novel, causal role for dynamic DAN activity unfolding over seconds-long timescales in controlling the moment-by-moment decision of when to move.
Competing Interest Statement
J.A.A. is a co-founder of OptogeniX, which produces the tapered optical fibers used in some experiments.
Footnotes
Supplementary Figure 3 panels added with reprint permission from AAAS.