Among the brainstem raphe nuclei, the dorsal raphe nucleus (DR) contains the greatest number of Pet1-lineage neurons, a predominantly serotonergic group distributed throughout DR subdomains. These neurons collectively regulate diverse physiology and behavior and are often therapeutically targeted to treat affective disorders. Characterizing Pet1 neuron molecular heterogeneity and relating it to anatomy is vital for understanding DR functional organization, with potential to inform therapeutic separability. Here we use high-throughput and DR subdomain-targeted single-cell transcriptomics and intersectional genetic tools to map molecular and anatomical diversity of DR-Pet1 neurons. We describe up to fourteen neuron subtypes, many showing biased cell body distributions across the DR. We further show that P2ry1-Pet1 DR neurons − the most molecularly distinct subtype − possess unique efferent projections and electrophysiological properties. These data complement and extend previous DR characterizations, combining intersectional genetics with multiple transcriptomic modalities to achieve fine-scale molecular and anatomic identification of Pet1 neuron subtypes.

中文翻译：

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小鼠背缝Pet1神经元的单细胞转录和解剖图集

在脑干沟核中，背沟核（DR）包含最多的Pet1谱系神经元，这是分布在整个DR亚域的主要是血清素能组。这些神经元共同调节各种生理和行为，并且通常在治疗上针对情感障碍。表征Pet1神经元分子异质性并将其与解剖学联系对于理解DR功能组织至关重要，并且具有告知治疗可分离性的潜力。在这里，我们使用高通量和针对DR亚域的单细胞转录组学和交叉遗传工具来绘制DR Pet1的分子和解剖多样性图神经元。我们描述了多达十四种神经元亚型，许多亚型在DR上显示出偏向的细胞体分布。我们进一步表明，P2ry1 - Pet1 DR神经元-分子上最不同的亚型-具有独特的传出投射和电生理特性。这些数据补充并扩展了先前的DR表征，将交叉遗传学与多种转录组学模式相结合，实现了Pet1神经元亚型的精细分子和解剖学鉴定。