Laboratory of Neurogenetics, Transgenic Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.
Laboratory for Integrative Neuroscience, Section on Synaptic Pharmacology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, 20852, USA.
Sci Rep. 2017 Jul 13;7(1):5283. doi: 10.1038/s41598-017-05598-1.
Aldehyde dehydrogenase 1 (ALDH1A1)-positive dopaminergic (DA) neurons at the ventral substantia nigra pars compacta (SNpc) preferentially degenerate in Parkinson's disease (PD). Their projection pattern and dopamine release properties, however, remains uncharacterized. Here we show that ALDH1A1-positive axons project predominantly to the rostral two-thirds of dorsal striatum. A portion of these axons converge on a small fraction of striosome compartments restricted to the dorsolateral striatum (DLS), where less dopamine release was measured compared to the adjacent matrix enriched with the ALDH1A1-negative axons. Genetic ablation of Aldh1a1 substantially increases the dopamine release in striosomes, but not in matrix. Additionally, the presence of PD-related human α-synuclein A53T mutant or dopamine transporter (DAT) blockers also differentially affects the dopamine output in striosomes and matrix. Together, these results demonstrate distinct dopamine release characteristics of ALDH1A1-positive DA fibers, supporting a regional specific function of ALDH1A1 in regulating dopamine availability/release in striatum.
乙醛脱氢酶 1（ALDH1A1）阳性多巴胺能（DA）神经元优先在帕金森病（PD）中于腹侧黑质致密部（SNpc）退化。然而，它们的投射模式和多巴胺释放特性仍未被描述。在这里，我们显示 ALDH1A1 阳性轴突主要投射到背侧纹状体的前三分之二。这些轴突的一部分汇聚在一小部分局限于背外侧纹状体（DLS）的纹状体隔室上，与富含 ALDH1A1 阴性轴突的相邻基质相比，这里测量到的多巴胺释放较少。Aldh1a1 的基因缺失会显著增加纹状体中的多巴胺释放，但不会增加基质中的多巴胺释放。此外，存在与 PD 相关的人α-突触核蛋白 A53T 突变体或多巴胺转运体（DAT）阻滞剂也会以不同的方式影响纹状体和基质中的多巴胺输出。总之，这些结果表明 ALDH1A1 阳性 DA 纤维具有独特的多巴胺释放特征，支持 ALDH1A1 在调节纹状体中多巴胺可用性/释放方面的区域特异性功能。
