The subthalamic nucleus (STN) is crucial for normal motor, limbic and associative function. STN dysregulation is correlated with several brain disorders, including Parkinsonʼs disease and obsessive compulsive disorder (OCD), for which high-frequency stimulation of the STN is increasing as therapy. However, clinical progress is hampered by poor knowledge of the anatomical–functional organization of the STN. Today, experimental mouse genetics provides outstanding capacity for functional decoding, provided selective promoters are available. Here, we implemented single-nuclei RNA sequencing (snRNASeq) of the mouse STN followed through with histological analysis of 16 candidate genes of interest. Our results demonstrate that the mouse STN is composed of at least four spatio-molecularly defined domains, each distinguished by defined sets of promoter activities. Further, molecular profiles dissociate the STN from the adjoining para-STN (PSTN) and neighboring structures of the hypothalamus, mammillary nuclei and zona incerta. Enhanced knowledge of STN´s internal organization should prove useful towards genetics-based functional decoding of this clinically relevant brain structure.

丘脑下核（STN）对于正常的运动，边缘和联想功能至关重要。STN失调与多种脑部疾病相关，包括帕金森氏病和强迫症（OCD），对此，STN的高频刺激随着治疗而增加。但是，由于对STN的解剖功能组织的了解不足，阻碍了临床进展。今天，实验小鼠遗传学提供了出色的功能解码能力，前提是可以使用选择性启动子。在这里，我们实施了小鼠STN的单核RNA测序（snRNASeq），然后对16个候选候选基因进行了组织学分析。我们的研究结果表明，小鼠STN由至少四个时空分子定义的域组成，每个都通过定义的启动子活动集来区分。此外，分子特征使STN与相邻的对STN（PSTN）和下丘脑，乳突和不透明带的邻近结构分离。对STN内部组织的增强了解应该证明对这种临床相关脑结构的基于遗传学的功能解码很有用。