Abstract
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 substantia nigra pas compacta 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.
Highlights
Parkinson’s disease (PD), the most common degenerative movement disorder, affects basal ganglia dopamine transmission (Sulzer and Surmeier, 2013; Vogt Weisenhorn et al, 2016)
Dopamine replacement therapy is less effective in treating the PD patients with learning and memory deficiency (Emre, 2003; Heremans et al, 2016). These findings suggest that dynamic dopamine release from aldehyde dehydrogenase 1A1 (ALDH1A1)+ nDANs is a key requirement for the learning process (Helie et al, 2015)
Previous studies demonstrate that ALDH1A1+ nDANs are preferentially degenerated in PD, the most common degenerative movement disorder (Cai et al, 2014; Liu et al, 2014)
Summary
Parkinson’s disease (PD), the most common degenerative movement disorder, affects basal ganglia dopamine transmission (Sulzer and Surmeier, 2013; Vogt Weisenhorn et al, 2016). The nigrostriatal DANs are diverse in nature and can be categorized into groups of distinct subpopulations based on location, gene expression profiles, electrophysiological properties, morphology, projection pattern, physiological functions, and vulnerabilities to various diseases (Liu et al, 2014; Poulin et al, 2014; Lerner et al, 2015; Menegas et al, 2015; Evans et al, 2017; Hook et al, 2018).
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