Sympathetic functional units encoded by genetically defined postganglionic neurons

The sympathetic system connects the brain with internal organs through distinct functional pathways; however, our understanding of their organization is limited. Here, we employed genetic labeling and single-cell transcriptomic analysis and identified two molecularly defined subpopulations of celiac-superior mesenteric ganglia (CG-SMG) neurons that implement different sympathetic functional pathways. Calb2-positive CG-SMG neurons project exclusively to the muscular layer of the gastrointestinal tract, forming endings associated with myenteric ganglia. Conversely, Nxph4-positive neurons innervate blood vessels within multiple organs, creating perivascular endings. Functional manipulations demonstrated that Calb2-labeled sympathetic neurons regulate gut motility without affecting blood flow, whereas Nxph4-positive neurons act as visceral vasoconstrictors, regulating blood flow independently of gut motility. The selectively induced autonomic responses by these two transcriptionally distinct subsets of postganglionic neurons suggest that the sympathetic nervous system uses a labeled line logic to control organ physiology.