Autonomic Nerves

The autonomic nervous system consists of parasympathetic and sympathetic efferents. In the case of the gut, the vagus nerve provides efferent parasympathetic information to the small intestine and the proximal colon, while nerves within the pelvic ganglion provide information to the distal colon and rectum. Meanwhile, sympathetic neurons travel in splanchnic and pelvic nerves, with their cell bodies in pre-vertebral celiac, mesenteric and pelvic ganglia (Spencer et al. Nat Reviews Gastro & Hep, 2026).

Both sympathetic and parasympathetic nerves interact prominently with immune and connective tissue cells in their environment to regulate homeostasis and host defence (e.g. Udit et al., Nat Rev Neurosci, 2022, Yang et al. Cell Mol Immunol, 2023).

Transcriptionally, single cell or nuclear RNA sequencing datasets have been generated in rodents, with a recent review (Wang et al., Nat Neurosci, 2025) compiling some of these into an easily browsable web-resource. Most of them are not specifically focused on gut-innervating efferent fibres, although there is a rat dataset of celiac ganglion cells (Kanda et al., Sci Rep, 2025) and two mouse datasets of celiac and superior mesenteric ganglia (Wang et al., Nature, 2024, Wei et al., Neuron, 2026). In human, there are two papers which contain data on sympathetic ganglia, but they are not gut innervating ganglia, but rather stellate ganglion (Haberman et al., Immunity, 2024) and thoracolumbar paravertebral sympathetic ganglia (Yang et al. bioRxiv, 2026).

Regarding in vitro model systems, primary rodent sympathetic neurons can be cultured for short periods of time in the presence of nerve growth factor (NGF), a protocol originally established by Robert Campenot (PNAS, 1977). Since then, many articles have been published using this method (Zareen & Greene, J Vis Exp, 2009). However, these primary cultures usually derive from superior cervical ganglia, rather than the gut-relevant mesenteric and celiac ganglia. This is likely because most smaller sympathetic ganglia need extensive training to identify and dissect in rodents.

More recently, human stem-cell derived sympathetic (e.g. Wu et al., STAR protocols, 2024, Oh et al., Cell Stem Cell, 2016) and parasympathetic neuron protocols are being developed (e.g. James et al., STAR protocols, 2025, Thomas et al., bioRxiv, 2025). They have yet to be widely adopted, and as with any model system, some features of native cells will be represented, while others will not be.

Text by Franziska Denk, King’s College London