Department of Chemistry, Chevron Science Center, University of Pittsburgh, 219 Parkman Ave., Pittsburgh, PA, 15213, USA.
Anal Bioanal Chem. 2021 Nov;413(27):6703-6713. doi: 10.1007/s00216-021-03300-z. Epub 2021 Apr 12.
The neurochemical transmitter dopamine (DA) is implicated in a number of diseases states, including Parkinson's disease, schizophrenia, and drug abuse. DA terminal fields in the dorsal striatum and core region of the nucleus accumbens in the rat brain are organized as heterogeneous domains exhibiting fast and slow kinetic of DA release. The rates of dopamine release are significantly and substantially faster in the fast domains relative to the slow domains. The striatum is composed of a mosaic of spatial compartments known as the striosomes (patches) and the matrix. Extensive literature exists on the spatial organization of the patch and matrix compartments and their functions. However, little is known about these compartments as they relate to fast and slow kinetic DA domains observed by fast scan cyclic voltammetry (FSCV). Thus, we combined high spatial resolution of FSCV with detailed immunohistochemical analysis of these architectural compartments (patch and matrix) using fluorescence microscopy. Our findings demonstrated a direct correlation between patch compartments with fast domain DA kinetics and matrix compartments to slow domain DA kinetics. We also investigated the kinetic domains in two very distinct sub-regions in the striatum, the lateral dorsal striatum (LDS) and the medial dorsal striatum (MDS). The lateral dorsal striatum as opposed to the medial dorsal striatum is mainly governed by fast kinetic DA domains. These finding are highly relevant as they may hold key promise in unraveling the fast and slow kinetic DA domains and their physiological significance.
神经化学递质多巴胺（DA）与多种疾病状态有关，包括帕金森病、精神分裂症和药物滥用。大鼠大脑背侧纹状体和伏隔核核心区域的 DA 末梢场组织为异质域，表现出快速和慢速的 DA 释放动力学。与慢速域相比，快速域中 DA 的释放速度明显且显著更快。纹状体由称为纹状体（斑块）和基质的空间隔室的马赛克组成。关于斑块和基质隔室的空间组织及其功能，已经有大量文献报道。然而，关于这些隔室与快速扫描循环伏安法（FSCV）观察到的快速和慢速动力学 DA 域的关系，知之甚少。因此，我们将 FSCV 的高空间分辨率与使用荧光显微镜对这些结构隔室（斑块和基质）进行的详细免疫组织化学分析相结合。我们的研究结果表明，斑块隔室与快速域 DA 动力学之间存在直接相关性，而基质隔室与慢速域 DA 动力学之间存在直接相关性。我们还研究了纹状体中两个非常不同的亚区，即外侧背侧纹状体（LDS）和内侧背侧纹状体（MDS）中的动力学域。与内侧背侧纹状体相比，外侧背侧纹状体主要由快速动力学 DA 域控制。这些发现非常重要，因为它们可能为揭示快速和慢速动力学 DA 域及其生理意义提供关键的承诺。
