Max Planck Institute for Metabolism Research, Gleueler Str. 50, 50931, Cologne, Germany.
Department of Neurology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
Nat Commun. 2019 Jan 18;10(1):336. doi: 10.1038/s41467-018-08143-4.
To date, the spatiotemporal release of specific neurotransmitters at physiological levels in the human brain cannot be detected. Here, we present a method that relates minute-by-minute fluctuations of the positron emission tomography (PET) radioligand [11C]raclopride directly to subsecond dopamine release events. We show theoretically that synaptic dopamine release induces low frequency temporal variations of extrasynaptic extracellular dopamine levels, at time scales of one minute, that can evoke detectable temporal variations in the [11C]raclopride signal. Hence, dopaminergic activity can be monitored via temporal fluctuations in the [11C]raclopride PET signal. We validate this theory using fast-scan cyclic voltammetry and [11C]raclopride PET in mice during chemogenetic activation of dopaminergic neurons. We then apply the method to data from human subjects given a palatable milkshake and discover immediate and-for the first time-delayed food-induced dopamine release. This method enables time-dependent regional monitoring of stimulus-evoked dopamine release at physiological levels.
迄今为止，无法在生理水平上检测到人类大脑中特定神经递质的时空释放。在这里，我们提出了一种方法，可将正电子发射断层扫描（PET）示踪剂[11C]raclopride 的每分钟波动直接与亚秒级多巴胺释放事件相关联。我们从理论上表明，突触多巴胺释放会在一分钟的时间尺度上诱导细胞外多巴胺水平的低频时间变化，从而在[11C]raclopride 信号中引发可检测到的时间变化。因此，可以通过[11C]raclopride PET 信号的时间波动来监测多巴胺能活性。我们使用快速扫描循环伏安法和[11C]raclopride PET 在化学遗传激活多巴胺能神经元的小鼠中验证了这一理论。然后，我们将该方法应用于给予美味奶昔的人类受试者的数据，并发现了即时和（首次）延迟的食物诱导的多巴胺释放。该方法能够在生理水平上进行时间依赖性的区域刺激诱发多巴胺释放监测。
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