Department of Organismal Biology, Unit of Comparative Physiology, Uppsala University, SE-752 36, Uppsala, Sweden.
Oramacell, 75006, Paris, France.
Commun Biol. 2020 Jul 3;3(1):338. doi: 10.1038/s42003-020-1028-8.
The subthalamic nucleus (STN) is crucial for normal motor, limbic and associative function. STN dysregulation is correlated with several brain disorders, including Parkinson's 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.
底丘脑核（STN）对于正常的运动、边缘和联想功能至关重要。STN 失调与包括帕金森病和强迫症（OCD）在内的几种脑部疾病有关，对于这些疾病，STN 的高频刺激作为治疗方法正在增加。然而，由于对 STN 的解剖-功能组织知之甚少，临床进展受到阻碍。如今，实验小鼠遗传学提供了出色的功能解码能力，只要有选择性启动子即可。在这里，我们对小鼠 STN 进行了单细胞 RNA 测序（snRNASeq），随后对 16 个感兴趣的候选基因进行了组织学分析。我们的结果表明，小鼠 STN 至少由四个空间分子定义的域组成，每个域都由定义明确的启动子活性集来区分。此外，分子特征将 STN 与毗邻的副 STN（PSTN）以及下丘脑、乳头核和未定带的邻近结构区分开来。增强对 STN 内部组织的了解，对于基于遗传学的对这一临床相关脑结构的功能解码应该是有用的。
