Organ-specific sympathetic innervation defines visceral functions

Nature. 2024 Nov 27. doi: 10.1038/s41586-024-08269-0. Online ahead of print.

Abstract

The autonomic nervous system orchestrates the functions of the brain and body through the sympathetic and parasympathetic pathways1. However, our understanding of the autonomic system, especially the sympathetic system, at the cellular and molecular levels is severely limited. Here we show topological representations of individual visceral organs in the major abdominal sympathetic ganglion complex. Using multi-modal transcriptomic analyses, we identified molecularly distinct sympathetic populations in the coeliac-superior mesenteric ganglia (CG-SMG). Of note, individual CG-SMG populations exhibit selective and mutually exclusive axonal projections to visceral organs, targeting either the gastrointestinal 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 regulates gastrointestinal transit, and another class of neurons controls digestion and glucagon secretion independent of gut motility. These results reveal the molecularly diverse sympathetic system and suggest modular regulation of visceral organ functions by sympathetic populations.