Function and Regulation of ALDH1A1-Positive Nigrostriatal Dopaminergic Neurons in Motor Control and Parkinson's Disease.

Function and Regulation of ALDH1A1-Positive Nigrostriatal Dopaminergic Neurons in Motor Control and Parkinson's Disease.
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DOI:
10.3389/fncir.2021.644776
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发表时间:
2021
影响因子:
3.5
通讯作者:
Cai H
Cai H
中科院分区:
医学3区
文献类型:
--
作者:
Carmichael K;Evans RC;Lopez E;Sun L;Kumar M;Ding J;Khaliq ZM;Cai H

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多巴胺是大脑中重要的化学信使,它调节运动、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,我们集中讨论一个小的,但独特的一组多巴胺产生的神经元,显示最深刻的损失,在腹侧黑质的帕金森氏病患者。这组多巴胺能神经元可以通过选择性表达醛脱氢酶1A1(ALDH1A1)容易地鉴定,并且占人和小鼠脑中总黑质纹状体多巴胺能神经元的70%。最近,我们提出了这些ALDH1A1阳性多巴胺能神经元的第一个全脑电路图,并揭示了这些神经元在获得运动技能过程中调节运动活力的重要生理功能。在这篇综述中,我们首先总结了ALDH1A1阳性黑质纹状体多巴胺能神经元及其连接和功能的研究结果,然后提供了关于ALDH1A1阳性黑质纹状体多巴胺能神经元的活性是如何通过整合不同的突触前输入及其对潜在的帕金森病治疗的影响进行调节的观点。
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.
基底神经节抑制输入对黑质多巴胺能神经元的功能剖析。
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