Poulin Jean-Francois, Caronia Giuliana, Hofer Caitlyn, Cui Qiaoling, Helm Brandon, Ramakrishnan Charu, Chan C Savio, Dombeck Daniel A, Deisseroth Karl, Awatramani Rajeshwar
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Nat Neurosci. 2018 Sep;21(9):1260-1271. doi: 10.1038/s41593-018-0203-4. Epub 2018 Aug 13.
Midbrain dopamine (DA) neurons have diverse functions that can in part be explained by their heterogeneity. Although molecularly distinct subtypes of DA neurons have been identified by single-cell gene expression profiling, fundamental features such as their projection patterns have not been elucidated. Progress in this regard has been hindered by the lack of genetic tools for studying DA neuron subtypes. Here we develop intersectional genetic labeling strategies, based on combinatorial gene expression, to map the projections of molecularly defined DA neuron subtypes. We reveal distinct genetically defined dopaminergic pathways arising from the substantia nigra pars compacta and from the ventral tegmental area that innervate specific regions of the caudate putamen, nucleus accumbens and amygdala. Together, the genetic toolbox and DA neuron subtype projections presented here constitute a resource that will accelerate the investigation of this clinically significant neurotransmitter system.
中脑多巴胺（DA）神经元具有多种功能，其异质性可部分解释这些功能。尽管通过单细胞基因表达谱分析已鉴定出分子上不同的DA神经元亚型，但其诸如投射模式等基本特征尚未阐明。由于缺乏用于研究DA神经元亚型的遗传工具，这方面的进展受到了阻碍。在此，我们基于组合基因表达开发了交叉遗传标记策略，以绘制分子定义的DA神经元亚型的投射图谱。我们揭示了源自黑质致密部和腹侧被盖区的不同的基因定义的多巴胺能通路，这些通路支配尾状壳核、伏隔核和杏仁核的特定区域。本文介绍的遗传工具箱和DA神经元亚型投射共同构成了一种资源，将加速对这个具有临床意义的神经递质系统的研究。
