Taylor I Mitch, Nesbitt Kathryn M, Walters Seth H, Varner Erika L, Shu Zhan, Bartlow Kathleen M, Jaquins-Gerstl Andrea S, Michael Adrian C
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
J Neurochem. 2015 May;133(4):522-31. doi: 10.1111/jnc.13059. Epub 2015 Mar 13.
Dopamine (DA), a highly significant neurotransmitter in the mammalian central nervous system, operates on multiple time scales to affect a diverse array of physiological functions. The significance of DA in human health is heightened by its role in a variety of pathologies. Voltammetric measurements of electrically evoked DA release have brought to light the existence of a patchwork of DA kinetic domains in the dorsal striatum (DS) of the rat. Thus, it becomes necessary to consider how these domains might be related to specific aspects of DA's functions. Responses evoked in the fast and slow domains are distinct in both amplitude and temporal profile. Herein, we report that responses evoked in fast domains can be further classified into four distinct types, types 1-4. The DS, therefore, exhibits a total of at least five distinct evoked responses (four fast types and one slow type). All five response types conform to kinetic models based entirely on first-order rate expressions, which indicates that the heterogeneity among the response types arises from kinetic diversity within the DS terminal field. We report also that functionally distinct subregions of the DS express DA kinetic diversity in a selective manner. Thus, this study documents five response types, provides a thorough kinetic explanation for each of them, and confirms their differential association with functionally distinct subregions of this key DA terminal field. The dorsal striatum is composed of five significantly different dopamine domains (types 1-4 and slow, average ± SEM responses to medial forebrain bundle (MFB) stimulation are shown in the figure). Responses from each of these five domains exhibit significantly different ascending and descending kinetic profiles and return to a long lasting elevated dopamine state, termed the dopamine hang-up. All features of these responses are modeled with high correlation using first-order modeling as well as our recently published restricted diffusion model of evoked dopamine overflow. We also report that functionally distinct subregions of the dorsal striatum express selective dopamine kinetic diversity.
多巴胺（DA）是哺乳动物中枢神经系统中一种非常重要的神经递质，在多个时间尺度上发挥作用，影响多种生理功能。DA在人类健康中的重要性因其在多种病理状态中的作用而得到增强。对电诱发DA释放的伏安测量揭示了大鼠背侧纹状体（DS）中存在DA动力学域的拼凑情况。因此，有必要考虑这些域如何与DA功能的特定方面相关。在快速和慢速域中诱发的反应在幅度和时间分布上都有所不同。在此，我们报告在快速域中诱发的反应可进一步分为四种不同类型，即1 - 4型。因此，DS总共表现出至少五种不同的诱发反应（四种快速类型和一种慢速类型）。所有五种反应类型都符合完全基于一级速率表达式的动力学模型，这表明反应类型之间的异质性源于DS终末场中的动力学多样性。我们还报告说，DS功能上不同的亚区域以选择性方式表达DA动力学多样性。因此，本研究记录了五种反应类型，为每种类型提供了全面的动力学解释，并证实了它们与这个关键DA终末场功能上不同的亚区域的差异关联。背侧纹状体由五个显著不同的多巴胺域组成（图中显示了对内侧前脑束（MFB）刺激的1 - 4型和慢速的平均±标准误反应）。这五个域中每个域的反应都表现出显著不同的上升和下降动力学曲线，并恢复到一种持久的多巴胺升高状态，称为多巴胺滞留。这些反应的所有特征都使用一级建模以及我们最近发表的诱发多巴胺溢出的受限扩散模型进行了高度相关的建模。我们还报告说，背侧纹状体功能上不同的亚区域表达选择性多巴胺动力学多样性。
