Organ-specific sympathetic innervation defines visceral functions, 2024, Wang et al.

[SNT Gatchaman]

Organ-specific sympathetic innervation defines visceral functions
Wang, Tongtong; Teng, Bochuan; Yao, Dickson R.; Gao, Wei; Oka, Yuki

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.

Link | PDF (Nature)

 

[SNT Gatchaman]

(In mice)

Introduction —

The sympathetic nervous system in vertebrate animals is generally activated under stress and mediates adrenergic ‘fight or flight’ responses by increasing heart rate and blood glucose level while suppressing digestion and body fluid secretion. The parasympathetic system counteracts the actions of the sympathetic system. A few recent studies have identified genetically distinct parasympathetic pathways to cardiovascular and gastrointestinal areas. Although the anatomy of the sympathetic system has been well described, its molecular and functional organization remains largely unknown. This lack of basic understanding poses a challenge in developing targeted therapeutic interventions for autonomic disorders such as irritable bowel syndrome and gastroparesis. Current treatments rely largely on nonspecific modulation of neurotransmitters identified over a century ago.

Concluding —

Various models have been proposed to explain how the sympathetic nervous system regulates peripheral organs. One such model is a uniform regulation in which visceral functions are ubiquitously controlled by the sympathetic system44,45 . Another model has suggested that different organs are controlled by distinct sympathetic populations. Our study strongly favours the latter model: CG–SMG RXFP1 and CG–SMGSHOX2 neurons exhibited complementary projection patterns with distinct functions.

CG–SMG RXFP1 neurons project to secretory sites (the bile duct, duodenum, pancreas and liver), whereas CG–SMG SHOX2 neurons send innervations to the visceral gastrointestinal tract. Our functional perturbation experiments supported separate functions between these populations for controlling bile and glucagon secretion versus gastrointestinal transit. Further analyses are required to determine whether each CG–SMG population contributes to other visceral functions, and how specific tissues and layers within the same organ are innervated by sympathetic populations.