GSE201998
Single-nuclei RNA sequencing of the locus coeruleus and pericoerulear brain regions
As the primary source of norepinephrine (NE) in the brain, the locus coeruleus (LC) regulates both arousal and stress responses, but how neuromodulatory inputs contribute to LC modulation remains incompletely understood. In this study, we isolated a network of transcriptionally diverse inhibitory pericoerulear (peri-LC) GABAergic neurons that integrate distant stimuli and modulate modes of LC firing. To define the peri-LC anatomy, we used viral tracing, single-nuclei and high-resolution spatial RNA transcriptomics to molecularly characterize both LC and peri-LC cell types. We complemented this approach with techniques in electrophysiology, photometry, optogenetics, and chemogenetics to probe the function of peri-LC neurons in behaving mice. These findings indicate that LC and peri-LC neurons comprise transcriptionally heterogenous neuronal groups which integrate diverse inputs to influence behavioral arousal states and avoidance. We used snRNAseq to characterize the peri-LC and LC brain regions. Our dataset contains 30,838 cells, of which 12,278 are neurons. Overall design: We microdissect the LC and peri-LC brain regions in wild type adult male and female mice, dissociated the nuclei, captured single nuclei transcriptomes via Chromium technology developed by 10X Genomics, and generated cDNA for sequencing.