Influence of phasic and tonic dopamine release on receptor activation.
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 D(1) and D(2) 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 D(1) receptors, whereas pauses translate into low occupancy of D(1) and D(2) receptors. Phasic firing patterns, composed of bursts and pauses, reduce the average D(2) receptor occupancy and increase average D(1) 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.
Department for Neuroscience and Pharmacology, University of Copenhagen, DK-2200 Copenhagen, Denmark. jakobdr@sund.ku.dk
Jakob K
JK
Dreyer
Kjartan F
KF
Herrik
Rune W
RW
Berg
Jørn D
JD
Hounsgaard
D000465:Algorithms; D001369:Axons / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism; D007700:Kinetics; D008959:Models, Neurological; D015233:Models, Statistical; D009411:Nerve Endings / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004298:Dopamine