Hamilos, A. E. | Search bioRxiv

bioRxiv2020

Application of a unifying reward-prediction error (RPE)-based framework to explain underlying dynamic dopaminergic activity in timing tasks

Dopaminergic neurons (DANs) exhibit complex dynamics across a variety of behavioral contexts, often in ways that seem task-specific and even incompatible with results across different paradigms. Dopaminergic signaling during timing tasks has been a prime example. In behavioral timing, dopaminergic dynamics predict the initiation of self-timed movement via a seconds-long ramp up of activity prior to movement onset, similar to ramping seen in visuospatial reward approach and multi-step, goal-directed behaviors. By contrast, in perceptual timing, DANs exhibit more complex dynamics whose direction of modulation seems to be the opposite of that observed in behavioral timing. Mikhael et al. (2022) recently proposed a formal model in which dopaminergic dynamics encode reward expectation in the form of an "ongoing" reward-prediction error (RPE) that arises from resolving uncertainty of ones position in the value landscape (i.e., ones spatial-temporal distance to reward delivery/omission). Here, we show that application of this framework recapitulates and reconciles the seemingly contradictory dopaminergic dynamics observed in behavioral vs perceptual timing. These results suggest a common neural mechanism that broadly underlies timing behavior: trial-by-trial variation in the rate of the internal "pacemaker," manifested in DAN signals that reflect stretching or compression of the derivative of the subjective value function relative to veridical time. In this view, faster pacemaking is associated with relatively high amplitude dopaminergic signaling, whereas slower pacemaking is associated with relatively low levels of dopaminergic signaling, consistent with findings from pharmacological and lesion studies.

animal behavior and cognition↗

bioRxiv2020

Dynamic dopaminergic activity controls the timing of self-timed movement

Clues from human movement disorders have long suggested that the neurotransmitter dopamine plays a key role in motor control, but how the endogenous dopaminergic system regulates movement is unknown. Here we show dynamic dopaminergic signaling over seconds-long timescales controls movement timing in mice. Animals were trained to initiate licking after a self-timed interval following a start-timing cue. 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 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. These results reveal a causal role for dynamic dopaminergic signaling unfolding over seconds in modulating the decision of when to move.

neuroscience↗