The autonomic nervous system arranges the functions of internal organs and acts as a link between the brain and the body. These functions are classified as sympathetic and parasympathetic pathways, which are often classified as accelerator and brake, respectively.
However, our current understanding of the autonomic system, especially the sympathetic system, is severely limited. We know the sympathetic nervous system responds to stimuli via the “fight-or-flight” response. For instance, during danger, it prioritizes energy utilization for critical operations over less urgent functions like digestion.
In a 2022 study, a team of academics found a system that transmits signals about hydration levels from the body to the brain. Yet, the actual mechanism that regulates these functions was not holistically explored.
A new study by Caltech researchers, published in Nature, uncovers diverse neurons within the sympathetic nervous system that coordinate the brain and body to maintain a healthy internal balance. This new study challenges the earlier view that the sympathetic nervous system is only a uniform network that controls organ functions.
“The anatomy and function of the autonomic system has been known for over a century, but we have surprisingly little understanding of cellular and functional diversity of autonomic neurons,” says Yuki Oka.
Unlike the central nervous system, which comprises neurons in the brain and spinal cord, the sympathetic nervous system ingrains neurons in ganglia throughout the body. Even though advanced computer simulations offer a deep look into the brain, examining autonomic neurons in the periphery is challenging.
To properly examine the gene expression patterns of cells in the major sympathetic ganglia, the team utilized single-cell RNA sequencing and spatial transcriptomic analysis. Experimenters discovered two distinct neuron populations with different sets of genes.
One of the neuronal groups targets the gastrointestinal tract, while the other covers the pancreas and bile tract.
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“Discovering the diverse sympathetic neuron populations with organ-specific innervation was electrifying, because it allows for precise control and modulation of body functions,” says the lead author Tongtong Wang.
To further study their influence on physiological processes, researchers turned their eyes on bile juice from the liver. In genetically modified mice, researchers used a few advanced tools. They found that one sympathetic neuron class suppresses digestive secretion and increases the release of glucagon to tune with the body’s immediate needs.
Meanwhile, the other neuron class independently carried out the gut motility. The lead author mentions it “like flipping switches in a complex machine and watching how each part responds.“
“The modular arrangement we uncovered means that the body can fine-tune each organ’s activity without affecting others. It’s a level of control that we did not fully appreciate before,” says Oka.
Though the sympathetic nervous system is well-known for responding to threats, this new study reveals that new stressors, like low glucose, can also trigger sympathetic neurons. With this discovery, researchers assert new avenues for disease treatment.
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Journal Reference
- Wang, T., Teng, B., Yao, D. R., Gao, W., & Oka, Y. (2024). Organ-specific sympathetic innervation defines visceral functions. Nature, 1-8. DOI: 10.1038/s41586-024-08269-0