Anxiety-related cell-type-specific neural circuits in the anterior-dorsal bed nucleus of the stria terminalis

Abstract The bed nucleus of the stria terminalis (BNST) plays a critical role in regulating anxiety, yet the involved specific cell types and their connections functioning in anxiety-related behaviors remains elusive. Here we identified two cell subpopulations—corticotropin-releasing hormone-positive (CRH+) and protein kinase C-δ-positive (PKC-δ+) neurons—each displayed discrete emotionally valenced behaviors in the anterior-dorsal BNST (adBNST). Using whole-cell patch-clamp recordings and virus-assisted circuit tracing techniques, we delineated the local and long-range connectivity networks in a cell-type-specific manner. The results show that the CRH+ and PKC-δ+ neurons received inputs from similar brain regions and exhibited significant differences in the downstream projection density. In addition, in vivo calcium imaging as well as gain- and loss-of-function studies characterized the physiological response properties and the functional heterogeneities in modulating anxiety, further suggesting the similarity and individuality between the two adBNST cell types. These results provide novel insights into the circuit architecture of adBNST neurons underlying the functionally specific neural pathways that relate to anxiety disorders.