Context-Dependent Multiplexing by Individual VTA Dopamine Neurons
Context-Dependent Multiplexing by Individual VTA Dopamine Neurons
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DOI：
10.1523/jneurosci.0502-20.2020
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发表时间：
2020-09-23
影响因子：
5.3
通讯作者：
Luescher, Christian
中科院分区：
文献类型：
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作者：
Kremer, Yves;Flakowski, Jerome;Luescher, Christian
腹侧被盖区的多巴胺（DA）神经元在巴甫洛夫条件反射过程中跟踪线索和奖励，以产生奖励预测误差信号。在这里，我们探索了这些神经元如何对自由移动的小鼠中的自定步调的操作性任务做出反应。动物可以通过在操作框的特定位置停留一段时间来触发奖励预测线索，然后移动到喷口收集奖励。使用携带对行为任务影响最小的光极的DAT-Cre雄性小鼠鉴定VTA DA神经元。在体内的单单位记录显示短暂的快速尖峰反应的线索和奖励在正确的试验，而不正确的活动暂停，反映积极和消极的错误信号的奖励预测。并行地，大多数VTA DA神经元同时编码多个动作（例如，运动速度、加速度、到目标的距离和舔）。应用GLM，我们表明，这种多重编码的奖励和运动变量的个别DA神经元是唯一明显的，而小鼠从事的任务。下游目标可以利用腹侧被盖区DA神经元的这种目标导向的多路复用来调整动作以优化任务的结果。
Dopamine (DA) neurons of the VTA track cues and rewards to generate a reward prediction error signal during Pavlovian conditioning. Here we explored how these neurons respond to a self-paced, operant task in freely moving mice. The animal could trigger a reward-predicting cue by remaining in a specific location of an operant box for a brief time before moving to a spout for reward collection. VTA DA neurons were identified using DAT-Cre male mice that carried an optrode with minimal impact on the behavioral task. In vivo single-unit recordings revealed transient fast spiking responses to the cue and reward in correct trials, while for incorrect ones the activity paused, reflecting positive and negative error signals of a reward prediction. In parallel, a majority of VTA DA neurons simultaneously encoded multiple actions (e.g., movement velocity, acceleration, distance to goal, and licking) in sustained slow firing modulation. Applying a GLM, we show that such multiplexed encoding of rewarding and motor variables by individual DA neurons was only apparent while the mouse was engaged in the task. Downstream targets may exploit such goal-directed multiplexing of VTA DA neurons to adjust actions to optimize the task's outcome.