Slowly evolving dopaminergic activity modulates the moment-to-moment probability of reward-related self-timed movements.
Slowly evolving dopaminergic activity modulates the moment-to-moment probability of reward-related self-timed movements.
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DOI：
10.7554/elife.62583
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发表时间：
2021-12-23
期刊：
影响因子：
7.7
通讯作者：
Assad JA
中科院分区：
文献类型：
--
作者：
Hamilos AE;Spedicato G;Hong Y;Sun F;Li Y;Assad JA
长期以来，人类运动障碍的线索表明，神经递质多巴胺在运动控制中发挥作用，但内源性多巴胺能系统如何影响运动尚不清楚。在这里，我们研究了多巴胺能信号和小鼠奖励相关运动的时间之间的关系。训练动物在开始计时提示后的自定时间间隔后开始舔;在标准时间后开始的运动中提供奖励。运动时间在不同试验中是可变的，正如先前研究所预期的那样。令人惊讶的是，多巴胺能信号在开始计时提示和自我计时运动之间的几秒钟内逐渐增加，并且在单次试验中预测运动/奖励时间的动态变化。急剧上升的信号出现在早期舔启动之前，而缓慢上升的信号出现在较晚的启动之前。更高的基线信号也预示着更早的自我定时运动。在自我计时过程中，多巴胺神经元的光遗传激活并没有引发立即的运动，而是引起了运动启动的系统性早期移位，而抑制引起了晚期移位，就好像调节运动的概率一样。与此观点相一致，内源性多巴胺能信号的动力学定量预测了单次试验中运动启动的每时每刻概率。我们提出，多巴胺能信号的斜坡，可能编码动态奖励期望，可以调节何时移动的决定。
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.