Department of Pharmacology and Chemical Biology, Emory University, Atlanta, GA 30322, USA.
Department of Neurology, Emory University, Atlanta, GA 30322, USA.
Cell Rep. 2023 Nov 28;42(11):113435. doi: 10.1016/j.celrep.2023.113435. Epub 2023 Nov 11.
The dorsal striatum is organized into functional territories defined by corticostriatal inputs onto both direct and indirect spiny projection neurons (SPNs), the major cell types within the striatum. In addition to circuit connectivity, striatal domains are likely defined by the spatially determined transcriptomes of SPNs themselves. To identify cell-type-specific spatiomolecular signatures of direct and indirect SPNs within dorsomedial, dorsolateral, and ventrolateral dorsal striatum, we used RNA profiling in situ hybridization with probes to >98% of protein coding genes. We demonstrate that the molecular identity of SPNs is mediated by hundreds of differentially expressed genes across territories of the striatum, revealing extraordinary heterogeneity in the expression of genes that mediate synaptic function in both direct and indirect SPNs. This deep insight into the complex spatiomolecular organization of the striatum provides a foundation for understanding both normal striatal function and for dissecting region-specific dysfunction in disorders of the striatum.
背侧纹状体组织成功能区域，由皮质纹状体输入定义，作用于直接和间接的棘突投射神经元（SPN），即纹状体中的主要细胞类型。除了回路连接，纹状体区域可能由 SPN 自身空间转录组来定义。为了确定背侧纹状体背内侧、背外侧和腹外侧的直接和间接 SPN 的细胞类型特异性空间分子特征，我们使用 RNA 原位杂交技术，使用 >98%的编码蛋白基因的探针。我们证明 SPN 的分子特征是由纹状体区域的数百个差异表达基因介导的，这揭示了直接和间接 SPN 中介导突触功能的基因表达具有非凡的异质性。这种对纹状体复杂空间分子组织的深入了解为理解正常纹状体功能以及剖析纹状体疾病中特定区域的功能障碍提供了基础。
