Institute for Neuroscience, University of Texas at Austin, Austin, TX, 78712, USA.
Department of Neuroscience, The University of Texas at Austin, Austin, TX, 78712, USA.
Transl Psychiatry. 2022 Jul 20;12(1):289. doi: 10.1038/s41398-022-02063-0.
The central amygdala (CeA) contains a diverse population of cells, including multiple subtypes of GABAergic neurons, along with glia and epithelial cells. Specific CeA cell types have been shown to affect alcohol consumption in animal models of dependence and may be involved in negative affect during alcohol withdrawal. We used single-nuclei RNA sequencing to determine cell-type specificity of differential gene expression in the CeA induced by alcohol withdrawal. Cells within the CeA were classified using unbiased clustering analyses and identified based on the expression of known marker genes. Differential gene expression analysis was performed on each identified CeA cell-type. It revealed differential gene expression in astrocytes and GABAergic neurons associated with alcohol withdrawal. GABAergic neurons were further subclassified into 13 clusters of cells. Analyzing transcriptomic responses in these subclusters revealed that alcohol exposure induced multiple differentially expressed genes in one subtype of CeA GABAergic neurons, the protein kinase C delta (PKCδ) expressing neurons. These results suggest that PKCδ neurons in the CeA may be uniquely sensitive to the effects of alcohol exposure and identify a novel population of cells in CeA associated with alcohol withdrawal.
中央杏仁核（CeA）包含多种细胞群体，包括多种 GABA 能神经元亚型，以及神经胶质细胞和上皮细胞。已证明特定的 CeA 细胞类型会影响依赖动物模型中的酒精消耗，并且可能与酒精戒断期间的负面情绪有关。我们使用单细胞核 RNA 测序来确定酒精戒断引起的 CeA 中差异基因表达的细胞类型特异性。使用无偏聚类分析对 CeA 内的细胞进行分类，并根据已知标记基因的表达来鉴定。对每个鉴定出的 CeA 细胞类型进行差异基因表达分析。结果显示，酒精戒断与星形胶质细胞和 GABA 能神经元的差异基因表达有关。GABA 能神经元进一步细分为 13 个细胞簇。分析这些亚簇中的转录组反应表明，酒精暴露在 CeA 的一种 GABA 能神经元亚型中诱导了多个差异表达基因，即蛋白激酶 C 德尔塔（PKCδ）表达神经元。这些结果表明 CeA 中的 PKCδ 神经元可能对酒精暴露的影响特别敏感，并确定了 CeA 中与酒精戒断相关的一个新的细胞群体。
