Floresco Stan B, West Anthony R, Ash Brian, Moore Holly, Grace Anthony A
Department of Neuroscienc, University of Pittsburgh, 446 Crawford Hall, Pittsburgh, Pennsylvania 15260, USA.
Nat Neurosci. 2003 Sep;6(9):968-73. doi: 10.1038/nn1103.
The mesolimbic dopamine system is centrally involved in reward and goal-directed behavior, and it has been implicated in multiple psychiatric disorders. Understanding the mechanism by which dopamine participates in these activities requires comprehension of the dynamics of dopamine release. Here we report dissociable regulation of dopamine neuron discharge by two separate afferent systems in rats; inhibition of pallidal afferents selectively increased the population activity of dopamine neurons, whereas activation of pedunculopontine inputs increased burst firing. Only the increase in population activity increased ventral striatal dopamine efflux. After blockade of dopamine reuptake, however, enhanced bursting increased dopamine efflux three times more than did enhanced population activity. These results provide insight into multiple regulatory systems that modulate dopamine system function: burst firing induces massive synaptic dopamine release, which is rapidly removed by reuptake before escaping the synaptic cleft, whereas increased population activity modulates tonic extrasynaptic dopamine levels that are less influenced by reuptake.
中脑边缘多巴胺系统在奖赏和目标导向行为中起核心作用，并且与多种精神疾病有关。要理解多巴胺参与这些活动的机制，需要了解多巴胺释放的动态过程。在此我们报告大鼠中两个独立传入系统对多巴胺神经元放电的不同调节；苍白球传入神经的抑制选择性地增加了多巴胺神经元的群体活动，而脚桥核输入的激活增加了爆发式放电。只有群体活动的增加会增加腹侧纹状体的多巴胺外流。然而，在多巴胺再摄取被阻断后，增强的爆发式放电使多巴胺外流增加的幅度是增强的群体活动的三倍。这些结果为调节多巴胺系统功能的多种调节系统提供了见解：爆发式放电诱导大量突触多巴胺释放，在其逸出突触间隙之前迅速被再摄取清除，而增加的群体活动调节受再摄取影响较小的持续性突触外多巴胺水平。
