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首页> 外文期刊>Journal of Neurophysiology >Dopamine-mediated volume transmission in midbrain is regulated by distinct extracellular geometry and uptake.
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Dopamine-mediated volume transmission in midbrain is regulated by distinct extracellular geometry and uptake.

机译：多巴胺介导的中脑体积传输受独特的细胞外几何形状和摄取调节。

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摘要

Somatodendritic release of dopamine (DA) in midbrain is, at least in part, nonsynaptic; moreover, midbrain DA receptors are predominantly extrasynaptic. Thus somatodendritic DA mediates volume transmission, with an efficacy regulated by the diffusion and uptake characteristics of the local extracellular microenvironment. Here, we quantitatively evaluated diffusion and uptake in substantia nigra pars compacta (SNc) and reticulata (SNr), ventral tegmental area (VTA), and cerebral cortex in guinea pig brain slices. The geometric parameters that govern diffusion, extracellular volume fraction (alpha) and tortuosity (lambda), together with linear uptake (k'), were determined for tetramethylammonium (TMA(+)), and for DA, using point-source diffusion combined with ion-selective and carbon-fiber microelectrodes. TMA(+)-diffusion measurements revealed a large alpha of 30% in SNc, SNr, and VTA, which was significantly higher than the 22% in cortex. Values for lambda and k' for TMA(+) were similar among regions. Point-source DA-diffusion curves fitted theory well with linear uptake, with significantly higher values of k' for DA in SNc and VTA (0.08--0.09 s(-1)) than in SNr (0.006 s(-1)), where DA processes are sparser. Inhibition of DA uptake by GBR-12909 caused a greater decrease in k' in SNc than in VTA. In addition, DA uptake was slightly decreased by the norepinephrine transport inhibitor, desipramine in both regions, although this was statistically significant only in VTA. We used these data to model the radius of influence of DA in midbrain. Simulated release from a 20-vesicle point source produced DA concentrations sufficient for receptor activation up to 20 microm away with a DA half-life at this distance of several hundred milliseconds. Most importantly, this model showed that diffusion rather than uptake was the most important determinant of DA time course in midbrain, which contrasts strikingly with the striatum where uptake dominates. The issues considered here, while specific for DA in midbrain, illustrate fundamental biophysical properties relevant for all extracellular communication.
机译：中脑多巴胺（DA）的体突性释放至少部分是非突触的。此外，中脑DA受体主要是突触外的。因此，树突状细胞DA介导体积传输，其功效受局部细胞外微环境的扩散和摄取特性调节。在这里，我们定量评估了豚鼠脑片中黑质致密部（SNc）和网状组织（SNr），腹侧被盖区（VTA）和大脑皮层的扩散和摄取。确定了控制扩散的几何参数，细胞外体积分数（α）和曲折度（lambda）以及线性吸收（k'），使用点源扩散法结合四甲基铵（TMA（+））和DA来确定离子选择性碳纤维微电极。 TMA（+）扩散测量结果显示，SNc，SNr和VTA的alpha值很高，为30％，大大高于皮质的22％。各地区之间TMA（+）的lambda和k'值相似。点源DA扩散曲线与线性吸收理论吻合得很好，SNc和VTA（0.08--0.09 s（-1））中DA的k'值明显高于SNr（0.006 s（-1））， DA流程稀疏的地方。与VTA相比，GBR-12909抑制DA吸收导致SNc中的k'降低更大。此外，去甲肾上腺素转运抑制剂地昔帕明在两个区域中的DA吸收均略有降低，尽管这仅在VTA中具有统计学意义。我们使用这些数据来模拟DA对中脑的影响半径。从20个囊泡点源的模拟释放产生的DA浓度足以使受体活化至20微米远，并且DA的半衰期为数百毫秒。最重要的是，该模型表明，扩散而不是摄取是中脑DA时程的最重要决定因素，这与摄取占主导地位的纹状体形成鲜明对比。这里考虑的问题，虽然特定于中脑的DA，但说明了与所有细胞外通讯相关的基本生物物理特性。

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