Transgenic Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States.
The Graduate Partnership Program of NIH and Brown University, National Institutes of Health, Bethesda, MD, United States.
Front Neural Circuits. 2021 May 17;15:644776. doi: 10.3389/fncir.2021.644776. eCollection 2021.
Dopamine is an important chemical messenger in the brain, which modulates movement, reward, motivation, and memory. Different populations of neurons can produce and release dopamine in the brain and regulate different behaviors. Here we focus our discussion on a small but distinct group of dopamine-producing neurons, which display the most profound loss in the ventral of patients with Parkinson's disease. This group of dopaminergic neurons can be readily identified by a selective expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and accounts for 70% of total nigrostriatal dopaminergic neurons in both human and mouse brains. Recently, we presented the first whole-brain circuit map of these ALDH1A1-positive dopaminergic neurons and reveal an essential physiological function of these neurons in regulating the vigor of movement during the acquisition of motor skills. In this review, we first summarize previous findings of ALDH1A1-positive nigrostriatal dopaminergic neurons and their connectivity and functionality, and then provide perspectives on how the activity of ALDH1A1-positive nigrostriatal dopaminergic neurons is regulated through integrating diverse presynaptic inputs and its implications for potential Parkinson's disease treatment.
多巴胺是大脑中一种重要的化学信使，调节运动、奖励、动机和记忆。不同的神经元群体可以在大脑中产生和释放多巴胺，并调节不同的行为。在这里，我们将重点讨论一小群但特征明显的多巴胺能神经元，它们在帕金森病患者的腹侧纹状体中表现出最显著的丧失。这群多巴胺能神经元可以通过醛脱氢酶 1A1（ALDH1A1）的选择性表达来轻易识别，占人类和小鼠大脑中总黑质纹状体多巴胺能神经元的 70%。最近，我们展示了这些 ALDH1A1 阳性多巴胺能神经元的全脑环路图谱，并揭示了这些神经元在调节运动技能获得过程中运动活力的重要生理功能。在这篇综述中，我们首先总结了以前关于 ALDH1A1 阳性黑质纹状体多巴胺能神经元及其连接和功能的发现，然后提供了关于 ALDH1A1 阳性黑质纹状体多巴胺能神经元的活动如何通过整合不同的突触前输入来调节的观点，以及其对潜在的帕金森病治疗的影响。
