Slowly evolving dopaminergic activity modulates the moment-to-moment probability of reward-related self-timed movements
- Harvard Medical School, United States
- Peking University School of Life Science, China
- Peiking University School of Life Sciences, China
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.
Data availability
All datasets supporting the findings of this study are publicly available (DOI: 10.5281/zenodo.4062749). Source data files have been provided for all figures.
Article and author information
Author details
Funding
National Institutes of Health (UF-NS108177)
- John Assad
National Institutes of Health (U19 NS113201)
- John Assad
National Institutes of Health (EY-12196)
- John Assad
Lefler Predoctoral Fellowship (n/a)
- Allison E Hamilos
Stuart H.Q. and Victoria Quan Predoctoral Fellowship (n/a)
- Allison E Hamilos
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments and protocols were approved by the Harvard Institutional Animal Care and Use Committee (IACUC protocol #05098, Animal Welfare Assurance Number #A3431-01) and were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Surgeries were conducted under aseptic conditions with isoflurane anesthesia, and every effort was taken to minimize suffering.
Copyright
© 2021, Hamilos et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Slowly evolving dopaminergic activity modulates the moment-to-moment probability of reward-related self-timed movements
eLife 10:e62583.
https://doi.org/10.7554/eLife.62583
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