Cragg Stephanie J, Hille Christopher J, Greenfield Susan A
University Department of Pharmacology, Oxford OX1 3QT, United Kingdom.
J Neurosci. 2002 Jul 1;22(13):5705-12. doi: 10.1523/JNEUROSCI.22-13-05705.2002.
The dorsal striatum comprises a continuum of distinct functional domains, limbic, associative, and sensorimotor. In the primate it exclusively subdivides further into two nuclei, the putamen and caudate. Dopamine (DA) transmission is differentially affected between these nuclei in neurodegenerative diseases such as Parkinson's and by psychostimulants such as cocaine. Because rodent systems can offer only limited insight into DA systems of the human brain, a fuller appreciation of DA transmission and its role in dysfunction requires direct study in primates. DA behavior was explored in the major functional domains of the caudate nucleus and compared with the putamen, using fast-scan cyclic voltammetry in striatal sections from the marmoset (Callithrix jacchus). There was domain-specific variation in extracellular DA transients [i.e., concentration (DA) released by a single stimulus and the rate maximum of DA uptake, V(max)]. Across nuclei, functional rather than anatomical regions were differentiated by these dynamics. The largest, fastest DA transients were at motor-associated loci. Evoked DA at physiological frequencies was differently frequency-sensitive between functional domains but not between anatomical nuclei. In contrast, presynaptic depression was not an index of regional differentiation, recovering with similar kinetics at all loci. Within a given functional domain of dorsal striatum, the dynamics of DA release and uptake are similar for the putamen and the caudate nucleus. Conversely, distinct functional domains are defined by these DA dynamics, in a manner more marked in primates than in rodents. These data from the primate brain highlight differences in DA availability that may be central to DA function and dysfunction in the human.
背侧纹状体由一系列不同的功能域组成,包括边缘系统、联合和感觉运动功能域。在灵长类动物中,它进一步专门细分为两个核,即壳核和尾状核。在帕金森氏症等神经退行性疾病以及可卡因等精神兴奋剂的作用下,多巴胺(DA)传递在这些核之间受到不同的影响。由于啮齿动物系统对人类大脑的DA系统提供的见解有限,因此要更全面地了解DA传递及其在功能障碍中的作用,需要在灵长类动物中进行直接研究。利用快速扫描循环伏安法,在狨猴(Callithrix jacchus)纹状体切片中,对尾状核的主要功能域中的DA行为进行了探索,并与壳核进行了比较。细胞外DA瞬变存在区域特异性变化[即单次刺激释放的浓度(DA)和DA摄取的最大速率V(max)]。通过这些动力学,区分的是功能区域而非解剖区域。最大、最快的DA瞬变出现在与运动相关的位点。在生理频率下诱发的DA在功能域之间对频率的敏感性不同,但在解剖核之间则没有差异。相比之下,突触前抑制不是区域分化的指标,在所有位点都以相似的动力学恢复。在背侧纹状体的给定功能域内,壳核和尾状核的DA释放和摄取动力学相似。相反,这些DA动力学定义了不同的功能域,在灵长类动物中比在啮齿动物中更为明显。来自灵长类动物大脑的这些数据突出了DA可用性的差异,这可能是人类DA功能和功能障碍的核心。