Sexually Dimorphic Cellular Architecture and Neural Circuity of ovBNST Proenkephalin Neurons
Limei Song1 · Yuqing Zhang1 · Mengqi Feng1 · Wenwen Su1 · Riming Zhu1 · Bin Zhang1 · Xia Zhang1,2 · Jie Li1
1 School of Basic Medicine, Neuropsychiatry Research Institute, The Afliated Hospital of Qingdao University, Qingdao University, Qingdao 266000, China
2 Department of Neurology, West China Hospital of Sichuan University, Chengdu 610041, China
Abstract
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 (ovBNSTPENK) neurons in male than female mice. Anatomically, we virally mapped the efferents and afferents of ovBNSTPENK neurons, finding reciprocally dimorphic connections with the hypothalamus and striatum. Gene enrichment analysis suggests that ovBNSTPENK neurons are modulated by the upstream dopamine pathway. Functionally, by applying caspase-3-mediated depletion of ovBNSTPENK 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 ovBNSTPENK neurons from a sexually dimorphic perspective.
Keywords
Sexual dimorphism; Proenkephalin; ovBNST; Striatum; Locomotion