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尾状核内多巴胺传递:多巴胺清除机制的区域变化和贡献。

Dopamine transmission in the tail striatum: Regional variation and contribution of dopamine clearance mechanisms.

机构信息

Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Department of Mechanical and Mechatronics Engineering, University of Auckland, Auckland, New Zealand.

出版信息

J Neurochem. 2024 Mar;168(3):251-268. doi: 10.1111/jnc.16052. Epub 2024 Feb 3.

DOI:10.1111/jnc.16052
PMID:38308566
Abstract

The striatum can be divided into four anatomically and functionally distinct domains: the dorsolateral, dorsomedial, ventral and the more recently identified caudolateral (tail) striatum. Dopamine transmission in these striatal domains underlies many important behaviours, yet little is known about this phenomenon in the tail striatum. Furthermore, the tail is divided anatomically into four divisions (dorsal, medial, intermediate and lateral) based on the profile of D and D dopamine receptor-expressing medium spiny neurons, something that is not seen elsewhere in the striatum. Considering this organisation, how dopamine transmission occurs in the tail striatum is of great interest. We recorded evoked dopamine release in the four tail divisions, with comparison to the dorsolateral striatum, using fast-scan cyclic voltammetry in rat brain slices. Contributions of clearance mechanisms were investigated using dopamine transporter knockout (DAT-KO) rats, pharmacological transporter inhibitors and dextran. Evoked dopamine release in all tail divisions was smaller in amplitude than in the dorsolateral striatum and, importantly, regional variation was observed: dorsolateral ≈ lateral > medial > dorsal ≈ intermediate. Release amplitudes in the lateral division were 300% of that in the intermediate division, which also exhibited uniquely slow peak dopamine clearance velocity. Dopamine clearance in the intermediate division was most dependent on DAT, and no alternative dopamine transporters investigated (organic cation transporter-3, norepinephrine transporter and serotonin transporter) contributed significantly to dopamine clearance in any tail division. Our findings confirm that the tail striatum is not only a distinct dopamine domain but also that each tail division has unique dopamine transmission characteristics. This supports that the divisions are not only anatomically but also functionally distinct. How this segregation relates to the overall function of the tail striatum, particularly the processing of multisensory information, is yet to be determined.

摘要

纹状体可分为四个解剖学和功能上不同的区域

背外侧、背内侧、腹侧和最近确定的尾侧(尾巴)纹状体。这些纹状体区域的多巴胺传递是许多重要行为的基础,但对尾状核中的这种现象知之甚少。此外,尾巴在解剖上分为四个部分(背、中、内侧和外侧),基于 D 和 D 多巴胺受体表达的中型多棘神经元的分布,这在纹状体的其他部位是看不到的。考虑到这种组织,尾状核中的多巴胺传递是如何发生的非常有趣。我们使用快速扫描循环伏安法在大鼠脑切片中记录了四个尾部分区的诱发多巴胺释放,并与背外侧纹状体进行了比较。使用多巴胺转运蛋白敲除(DAT-KO)大鼠、药理学转运蛋白抑制剂和葡聚糖研究了清除机制的贡献。所有尾部分区的诱发多巴胺释放幅度都小于背外侧纹状体,重要的是,观察到区域变化:背外侧≈外侧>内侧>背侧≈中间。外侧部分的释放幅度是中间部分的 300%,中间部分还表现出独特的慢峰多巴胺清除速度。中间部分的多巴胺清除最依赖于 DAT,而未研究的其他多巴胺转运蛋白(有机阳离子转运蛋白-3、去甲肾上腺素转运蛋白和 5-羟色胺转运蛋白)在任何尾部分区对多巴胺清除都没有显著贡献。我们的发现证实,尾状核不仅是一个独特的多巴胺区域,而且每个尾部分区都具有独特的多巴胺传递特征。这表明这些分区不仅在解剖学上而且在功能上也是不同的。这种分离与尾状核的整体功能(特别是多感觉信息的处理)有何关系,还有待确定。

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