Both phasic and tonic modes of neurotransmission are implicated in critical functions assigned to dopamine. In learning, for example, sub-second phasic responses of ventral tegmental area (VTA) dopamine neurons to salient events serve as teaching signals, but learning is also interrupted by dopamine antagonists administered minutes after training. Our findings bridge the multiple timescales of dopamine neurotransmission by demonstrating that burst stimulation of VTA dopamine neurons produces a prolonged post-burst increase (>20 min) of extracellular dopamine in nucleus accumbens and prefrontal cortex. This elevation is not due to spillover from the stimulation surge but depends on impulse flow-mediated dopamine release. We identified Rho-mediated internalization of dopamine transporter as a mechanism responsible for prolonged availability of actively released dopamine. Thus, a critical consequence of burst activity of dopamine neurons may be post-burst sustained elevation of extracellular dopamine in terminal regions via an intracellular mechanism that promotes dopamine transporter internalization. These results demonstrate that phasic and tonic dopamine neurotransmission can be a continuum and may explain why both modes of signaling are critical for motivational and cognitive functions associated with dopamine.

中文翻译：

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多巴胺神经元的爆发激活会导致爆发后主动释放的多巴胺的可用性延长。

神经传递的阶段性和强直性模式都与分配给多巴胺的关键功能有关。例如，在学习中，腹侧被盖区（VTA）多巴胺神经元对次要事件的亚秒级反应可作为教学信号，但在训练后数分钟内给予多巴胺拮抗剂也会中断学习。我们的发现通过证明VTA多巴胺神经元的突发刺激产生伏隔核和前额叶皮层中细胞外多巴胺的爆发后延长（> 20分钟）的延长，弥合了多巴胺神经传递的多个时间尺度。这种升高不是由于刺激浪涌引起的溢出，而是取决于脉冲流介导的多巴胺释放。我们确定Rho介导的多巴胺转运蛋白的内在化是负责主动释放多巴胺的延长可用性的机制。因此，多巴胺神经元爆发活动的关键后果可能是通过促进多巴胺转运蛋白内在化的细胞内机制，在末端区域爆发性持续升高的细胞外多巴胺。这些结果表明，多巴胺的阶段性和强直性神经传递可以是连续的，并且可以解释为什么两种信号传导方式对于与多巴胺相关的动机和认知功能都至关重要。多巴胺神经元爆发活动的一个关键后果可能是通过促进多巴胺转运蛋白内在化的细胞内机制在末端区域爆发后持续升高的细胞外多巴胺。这些结果表明，多巴胺的阶段性和强直性神经传递可以是连续的，并且可以解释为什么两种信号传导方式对于与多巴胺相关的动机和认知功能都至关重要。多巴胺神经元爆发活动的一个关键后果可能是通过促进多巴胺转运蛋白内在化的细胞内机制在末端区域爆发后持续升高的细胞外多巴胺。这些结果表明，多巴胺的阶段性和强直性神经传递可以是连续的，并且可以解释为什么两种信号传导方式对于与多巴胺相关的动机和认知功能都至关重要。