Song Limei, Zhang Yuqing, Feng Mengqi, Su Wenwen, Zhu Riming, Zhang Bin, Zhang Xia, Li Jie
School of Basic Medicine, Neuropsychiatry Research Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, 266000, China.
Department of Neurology, West China Hospital of Sichuan University, Chengdu, 610041, China.
Neurosci Bull. 2025 May 30. doi: 10.1007/s12264-025-01428-x.
Sexual dimorphism in the brain underlies behavioral differences between sexes. The bed nucleus of the stria terminalis (BNST) is a complex nucleus that differs between males and females, but the sexual dimorphism in cytoarchitecture and the connectome of its oval subdivision (ovBNST) remains largely unexplored. By combining snRNA-seq and transgenic labeling, we found a higher density of ovBNST proenkephalin (ovBNST) neurons in male than female mice. Anatomically, we virally mapped the efferents and afferents of ovBNST neurons, finding reciprocally dimorphic connections with the hypothalamus and striatum. Gene enrichment analysis suggests that ovBNST neurons are modulated by the upstream dopamine pathway. Functionally, by applying caspase-3-mediated depletion of ovBNST neurons, we found that loss of these neurons enhanced locomotor activity in male but not female mice, without altering the anxiety-like phenotypes in either sex. Our study may pave the way for a better understanding of the anatomical and functional profiles of ovBNST neurons from a sexually dimorphic perspective.
大脑中的性别二态性是两性行为差异的基础。终纹床核（BNST）是一个复杂的核团，在雄性和雌性之间存在差异，但其椭圆形亚区（ovBNST）的细胞结构和连接组中的性别二态性在很大程度上仍未被探索。通过结合单细胞核RNA测序（snRNA-seq）和转基因标记，我们发现雄性小鼠中ovBNST脑啡肽原（ovBNST）神经元的密度高于雌性小鼠。在解剖学上，我们通过病毒绘制了ovBNST神经元的传出和传入连接，发现与下丘脑和纹状体存在相互的二态性连接。基因富集分析表明，ovBNST神经元受上游多巴胺通路的调节。在功能上，通过应用caspase-3介导的ovBNST神经元缺失，我们发现这些神经元的缺失增强了雄性小鼠的运动活性，但对雌性小鼠没有影响，且两种性别的焦虑样表型均未改变。我们的研究可能为从性别二态性角度更好地理解ovBNST神经元的解剖和功能特征铺平道路。
