The cholinergic system in the brain plays crucial roles in regulating sensory and motor functions as well as cognitive behaviors by modulating neuronal activity. Understanding the organization of the cholinergic system requires a complete map of cholinergic neurons and their axon arborizations throughout the entire brain at the level of single neurons. Here, we report a comprehensive whole-brain atlas of the cholinergic system originating from various cortical and subcortical regions of the mouse brain. Using genetically labeled cholinergic neurons together with whole-brain reconstruction of optical images at 2-μm resolution, we obtained quantification of the number and soma volume of cholinergic neurons in 22 brain areas. Furthermore, by reconstructing the complete axonal arbors of fluorescently labeled single neurons from a subregion of the basal forebrain at 1-μm resolution, we found that their projections to the forebrain and midbrain showed neuronal subgroups with distinct projection specificity and diverse arbor distribution within the same projection area. These results suggest the existence of distinct subtypes of cholinergic neurons that serve different regulatory functions in the brain and illustrate the usefulness of complete reconstruction of neuronal distribution and axon projections at the mesoscopic level.

中文翻译：

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胆碱能系统全脑图谱的产生和基底前脑胆碱能神经元的介观投影分析

大脑中的胆碱能系统通过调节神经元活动在调节感觉和运动功能以及认知行为中起着至关重要的作用。了解胆碱能系统的组织要求在单个神经元水平上完整的胆碱能神经元及其轴突在整个大脑中的完整分布图。在这里，我们报告了源自小鼠大脑皮层和皮层下各个区域的胆碱能系统的全脑图谱。使用基因标记的胆碱能神经元和全脑重建2μm分辨率的光学图像，我们获得了22个脑区胆碱能神经元的数量和体细胞体积的量化信息。此外，通过以1μm的分辨率重建来自基底前脑子区域的荧光标记的单个神经元的完整轴突柄，我们发现它们对前脑和中脑的投影显示出神经元亚群，它们在同一投影区域内具有不同的投影特异性和不同的乔木分布。这些结果表明存在不同的胆碱能神经元亚型，这些亚型在大脑中具有不同的调节功能，并说明了在介观水平完全重建神经元分布和轴突投影的有用性。