Decoding molecular and cellular heterogeneity of nucleus accumbens with high-throughput scRNA-seq and MERFISH

Abstract The nucleus accumbens (NAc) plays an important role in regulating multiple behaviors and its dysfunction has been linked to many neural disorders. However, the molecular, cellular and anatomic heterogeneity underlying its functional diversity remains incompletely understood. Here, we generate a cell census of the mouse NAc using high-throughput single cell RNA sequencing and multiplexed error-robust FISH, revealing a high level of cell heterogeneity in this brain region. We show that the transcriptional and spatial diversity of neuron subtypes underlie NAc’s anatomic and functional heterogeneity, and possibly contribute to the pathogenesis of different neurological disorders. These findings explain how the seemingly simple neuronal composition of the NAc achieves its highly heterogenous structure and diverse functions. Collectively, our study generates a spatially resolved cell taxonomy for understanding the NAc structure and function, which demonstrates the importance of combining molecular and spatial information in revealing the fundamental features of the nervous system.