Influence of phasic and tonic dopamine release on receptor activation
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Influence of phasic and tonic dopamine release on receptor activation. / Dreyer, Jakob Kristoffer Kisbye; Herrik, Kjartan F; Berg, Rune W; Hounsgaard, Jørn D.
In: Journal of Neuroscience, Vol. 30, No. 42, 20.10.2010, p. 14273-83.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Influence of phasic and tonic dopamine release on receptor activation
AU - Dreyer, Jakob Kristoffer Kisbye
AU - Herrik, Kjartan F
AU - Berg, Rune W
AU - Hounsgaard, Jørn D
PY - 2010/10/20
Y1 - 2010/10/20
N2 - 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.
AB - 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.
KW - Algorithms
KW - Axons
KW - Corpus Striatum
KW - Dopamine
KW - Electrophysiology
KW - Extracellular Space
KW - Kinetics
KW - Models, Neurological
KW - Models, Statistical
KW - Nerve Endings
KW - Neurons
KW - Receptors, Dopamine
KW - Receptors, Dopamine D1
KW - Receptors, Dopamine D2
U2 - 10.1523/JNEUROSCI.1894-10.2010
DO - 10.1523/JNEUROSCI.1894-10.2010
M3 - Journal article
C2 - 20962248
VL - 30
SP - 14273
EP - 14283
JO - The Journal of neuroscience : the official journal of the Society for Neuroscience
JF - The Journal of neuroscience : the official journal of the Society for Neuroscience
SN - 0270-6474
IS - 42
ER -
ID: 33729312