Department for Neuroscience and Pharmacology, University of Copenhagen, DK-2200 Copenhagen, Denmark.
J Neurosci. 2010 Oct 20;30(42):14273-83. doi: 10.1523/JNEUROSCI.1894-10.2010.
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.
神经递质多巴胺的释放与学习、动机和运动功能有关。然而，多巴胺能神经元的尖峰模式、细胞外多巴胺浓度和多巴胺受体的激活之间的关系仍未得到解决。在本研究中，我们开发了一种多巴胺信号的计算模型，深入了解了释放和 D1 和 D2 受体占据的动力学之间的关系。该模型是从实验数据出发，基于第一性原理推导出来的，没有自由参数，可以对多巴胺容积传递的边界进行无偏估计。爆发主要增加 D1 受体的占据，而停顿则导致 D1 和 D2 受体的低占据。与等效的持续刺激相比，由爆发和停顿组成的相位刺激模式降低了平均 D2 受体占据，增加了平均 D1 受体占据。受体占据与同步性和持续与相位刺激模式之间的平衡密切相关。我们的结果提供了对容积传递动力学的定量理解，并补充了通过电生理学、正电子发射断层扫描、微透析、安培法和伏安法获得的实验数据。
