Influence of phasic and tonic dopamine release on receptor activation

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Jakob Kristoffer Kisbye Dreyer, Kjartan F Herrik, Rune W Berg, Jørn D Hounsgaard

Tonic and phasic dopamine release is implicated in learning, motivation, and motor functions. However, the relationship between spike patterns in dopaminergic neurons, the extracellular concentration of dopamine, and activation of dopamine receptors remains unresolved. In the present study, we develop a computational model of dopamine signaling that give insight into the relationship between the dynamics of release and occupancy of D1 and D2 receptors. The model is derived from first principles using experimental data. It has no free parameters and offers unbiased estimation of the boundaries of dopaminergic volume transmission. Bursts primarily increase occupancy of D1 receptors, whereas pauses translate into low occupancy of D1 and D2 receptors. Phasic firing patterns, composed of bursts and pauses, reduce the average D2 receptor occupancy and increase average D1 receptor occupancy compared with equivalent tonic firing. Receptor occupancy is crucially dependent on synchrony and the balance between tonic and phasic firing modes. Our results provide quantitative insight in the dynamics of volume transmission and complement experimental data obtained with electrophysiology, positron emission tomography, microdialysis, amperometry, and voltammetry.

TidsskriftJournal of Neuroscience
Udgave nummer42
Sider (fra-til)14273-83
Antal sider11
StatusUdgivet - 20 okt. 2010

ID: 33729312