Distinct Connectivity and Functionality of Aldehyde Dehydrogenase 1a1-Positive Nigrostriatal Dopaminergic Neurons in Motor Learning.
Distinct Connectivity and Functionality of Aldehyde Dehydrogenase 1a1-Positive Nigrostriatal Dopaminergic Neurons in Motor Learning.
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DOI：
10.1016/j.celrep.2019.06.095
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发表时间：
2019-07
期刊：
影响因子：
8.8
通讯作者：
Jun-bing Wu;Justin Kung;Jie Dong;Lisa Chang;Chengsong Xie;A. Habib;S. Hawes;Nannan Yang;Vivian C
中科院分区：
文献类型：
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作者：
Jun-bing Wu;Justin Kung;Jie Dong;Lisa Chang;Chengsong Xie;A. Habib;S. Hawes;Nannan Yang;Vivian C
帕金森病导致乙醛脱氢酶1A1阳性(ALDH1A1+)黑质纹状体多巴胺能神经元(NDAN)亚群的最严重损失。然而，ALDH1A1+nDAN的连接性和功能仍然知之甚少。在这里，我们显示在啮齿动物的大脑中，ALDH1A1+nDAN主要投射到嘴侧背侧纹状体，它们也从那里接受最多的单突触输入，表明与纹状体棘突投射神经元(SPN)广泛的相互支配。在功能上，ALDH1A1+nDAN的遗传消融导致运动技能学习的严重障碍，以及高速行走的减少。虽然多巴胺替代疗法加快了行走速度，但它未能改善ALDH1A1+NDAN消融小鼠的运动技能学习。综上所述，我们的研究提供了全面的全脑连接图，并揭示了ALDH1A1+nDAN在运动技能获得中的关键生理功能，表明运动学习过程需要ALDH1A1+nDAN整合不同的突触前输入，并以动态精确的方式提供多巴胺。
Parkinson's disease causes the most profound loss of the aldehyde dehydrogenase 1A1-positive (ALDH1A1+) nigrostriatal dopaminergic neuron (nDAN) subpopulation. The connectivity and functionality of ALDH1A1+nDANs, however, remain poorly understood. Here, we show in rodent brains that ALDH1A1+nDANs project predominantly to the rostral dorsal striatum, from which they also receive most monosynaptic inputs, indicating extensive reciprocal innervations with the striatal spiny projection neurons (SPNs). Functionally, genetic ablation of ALDH1A1+nDANs causes severe impairments in motor skill learning, along with a reduction in high-speed walking. While dopamine replacement therapy accelerated walking speed, it failed to improve motor skill learning in ALDH1A1+nDAN-ablated mice. Altogether, our study provides a comprehensive whole-brain connectivity map and reveals a key physiological function of ALDH1A1+nDANs in motor skill acquisition, suggesting the motor learning processes require ALDH1A1+nDANs to integrate diverse presynaptic inputs and supply dopamine with dynamic precision.