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

Author:

Hamilos Allison E1ORCID,Spedicato Giulia1,Hong Ye1,Sun Fangmiao2,Li Yulong3,Assad John1

Affiliation:

1. Department of Neurobiology, Harvard Medical School

2. State Key Laboratory of Membrane Biology, Peking University School of Life Science

3. State Key Laboratory of Membrane Biology, Peiking University School of Life Sciences

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.

Funder

National Institutes of Health

Lefler Predoctoral Fellowship

Stuart H.Q. and Victoria Quan Predoctoral Fellowship

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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