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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.

Original publication

DOI

10.1038/s41467-018-08143-4

Type

Journal article

Journal

Nat Commun

Publication Date

18/01/2019

Volume

10

Keywords

Animals, Brain, Dopamine, Eating, Electric Stimulation, Electrodes, Female, Humans, Male, Mice, Models, Biological, Neurons, Positron-Emission Tomography, Raclopride, Radioligand Assay, Temporal Lobe, Time Factors