Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, USA.
Sci Rep. 2024 Aug 6;14(1):18258. doi: 10.1038/s41598-024-69255-0.
Neural processing of rewarding stimuli involves several distinct regions, including the nucleus accumbens (NAc). The majority of NAc neurons are GABAergic projection neurons known as medium spiny neurons (MSNs). MSNs are broadly defined by dopamine receptor expression, but evidence suggests that a wider array of subtypes exist. To study MSN heterogeneity, we analyzed single-nucleus RNA sequencing data from the largest available rat NAc dataset. Analysis of 48,040 NAc MSN nuclei identified major populations belonging to the striosome and matrix compartments. Integration with mouse and human data indicated consistency across species and disease-relevance scoring using genome-wide association study results revealed potentially differential roles for MSN populations in substance use disorders. Additional high-resolution clustering identified 34 transcriptomically distinct subtypes of MSNs definable by a limited number of marker genes. Together, these data demonstrate the diversity of MSNs in the NAc and provide a basis for more targeted genetic manipulation of specific populations.
奖励性刺激的神经处理涉及几个不同的区域，包括伏隔核（NAc）。NAc 的大多数神经元是 GABA 能投射神经元，称为中型棘突神经元（MSNs）。MSNs 主要根据多巴胺受体表达来定义，但有证据表明存在更广泛的亚型。为了研究 MSN 的异质性，我们分析了来自最大的可用大鼠 NAc 数据集的单细胞 RNA 测序数据。对 48040 个 NAc MSN 核的分析确定了属于纹状体和基质隔室的主要群体。与小鼠和人类数据的整合表明了跨物种的一致性，并且使用全基因组关联研究结果进行疾病相关性评分表明，MSN 群体在物质使用障碍中可能具有不同的作用。额外的高分辨率聚类确定了 34 种具有有限数量标记基因的转录组不同的 MSN 亚型。总之，这些数据表明 NAc 中的 MSN 具有多样性，并为针对特定群体进行更有针对性的遗传操作提供了基础。
