Organ-specific Sympathetic Innervation Defines Visceral Functions

Abstract The autonomic nervous system orchestrates the brain and body functions through the sympathetic and parasympathetic pathways. However, our understanding of the autonomic system, especially the sympathetic system, at the cellular and molecular levels is severely limited. Here, we show unique topological representations of individual visceral organs in the major abdominal sympathetic ganglion complex. Using multi-modal transcriptomic analyses, we identified distinct sympathetic populations that are both molecularly and spatially separable in the celiac-superior mesenteric ganglia (CG-SMG). Notably, individual CG-SMG populations exhibit selective and mutually exclusive axonal projections to visceral organs, targeting either the gastrointestinal (GI) tract or secretory areas including the pancreas and bile tract. This combinatorial innervation pattern suggests functional segregation between different CG-SMG populations. Indeed, our neural perturbation experiments demonstrated that one class of neurons selectively regulates GI food transit. Another class of neurons controls digestion and glucagon secretion independent of gut motility. These results reveal the molecularly diverse sympathetic system and suggest modular regulations of visceral organ functions through distinct sympathetic populations.