The ventral tegmental area (VTA) is a critical node in circuits governing motivated behavior and is home to diverse populations of neurons that release dopamine, gamma-aminobutyric acid (GABA), glutamate, or combinations of these neurotransmitters. The VTA receives inputs from many brain regions, but a comprehensive understanding of input-specific activation of VTA neuronal subpopulations is lacking. To address this, we combined optogenetic stimulation of select VTA inputs with single-nucleus RNA sequencing (snRNA-seq) and highly multiplexed hybridization to identify distinct neuronal clusters and characterize their spatial distribution and activation patterns. Quantification of immediate-early gene (IEG) expression revealed that different inputs activated select VTA subpopulations, which demonstrated cell-type-specific transcriptional programs. Within dopaminergic subpopulations, IEG induction levels correlated with differential expression of ion channel genes. This new transcriptomics-guided circuit analysis reveals the diversity of VTA activation driven by distinct inputs and provides a resource for future analysis of VTA cell types.

中文翻译：

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Opto-seq揭示了腹侧被盖区细胞类型中输入特异性的立即早期基因诱导


腹侧被盖区 (VTA) 是控制动机行为的回路中的关键节点，是释放多巴胺、γ-氨基丁酸 (GABA)、谷氨酸或这些神经递质组合的多种神经元的所在地。 VTA 接收来自许多大脑区域的输入，但缺乏对 VTA 神经元亚群的输入特异性激活的全面了解。为了解决这个问题，我们将选择 VTA 输入的光遗传学刺激与单核 RNA 测序 (snRNA-seq) 和高度多重杂交相结合，以识别不同的神经元簇并表征其空间分布和激活模式。立即早期基因 (IEG) 表达的量化表明，不同的输入激活了选定的 VTA 亚群，这证明了细胞类型特异性的转录程序。在多巴胺能亚群中，IEG 诱导水平与离子通道基因的差异表达相关。这种新的转录组学引导的回路分析揭示了由不同输入驱动的 VTA 激活的多样性，并为未来分析 VTA 细胞类型提供了资源。