The human heart relies on a complex network of nerves to keep it functioning properly, but many details about these nerve connections remain unknown. Now, a team of scientists has made a major step in understanding this system by studying zebrafish, a small freshwater fish often used in research because of its similarities to human biology. Their study, published in the journal Nature Communications, provides new insights into how these nerves help regulate the heartbeat.
Dr. Caghan Kizil, and Dr. Konstantinos Ampatzis, from Columbia University and Karolinska Institutet, carried out an extensive investigation of these heart nerves. Using advanced genetic analysis, which examines DNA to understand how cells function, and electrical recording techniques, which measure the activity of nerve signals in the heart, they identified a surprising variety of nerve cells in the heart, including some that function similarly to the pacemaker cells, specialized cells that generate electrical impulses to maintain a steady heart rhythm. “Our findings reveal a wide range of nerve cell types in the heart, more than we previously thought existed,” said the researchers. Their study challenges the earlier belief that the heart’s nerve system merely transmits signals and instead shows it actively helps regulate the heartbeat.
The scientists identified different groups of nerve cells, each releasing different chemical messengers such as acetylcholine, a chemical that slows the heart rate; glutamate, a key neurotransmitter for nerve signaling; GABA, which helps regulate nervous system activity; serotonin, which influences mood and body functions; and adrenaline, a hormone that increases heart rate during stress. This suggests the heart’s nerves do more than just relay messages from the brain; they process information locally to fine-tune heart function. “The variety of nerve signals in the heart shows that these cells are actively involved in heart control rather than just passing along instructions,” the Dr. Kizil explained.
Their electrical recordings, which track nerve activity to understand how signals control the heart, showed that some of these nerve cells fire in rhythmic bursts, much like the pacemaker cells in the heart that set the heart rate. This suggests that the heart’s nerves do not just respond to signals from the brain but may actually help generate the heart’s rhythm. This is similar to other nerve networks, which are interconnected groups of neurons that coordinate movement and regulate rhythmic functions such as breathing and walking.
Dr. Kizil and Dr. Ampatzis’ findings are important beyond zebrafish. Because zebrafish hearts are similar in structure and function to human hearts, this study could help scientists understand how the human heart’s nerves contribute to heart regulation. This could lead to new ways to treat heart conditions linked to nerve dysfunction.
This research deepens our understanding of how the nervous system and the heart interact. It also opens the door to new approaches for treating heart diseases. As Dr. Ampatzis concluded, “The detailed classification of heart nerve cells we present here will be a valuable resource for future studies on heart function and heart-related diseases.”
Journal Reference
Pedroni A., Yilmaz E., Del Vecchio L., Bhattarai P., Talaya Vidal I., Dai Y-W. E., Koutsogiannis K., Kizil C., Ampatzis K. “Decoding the molecular, cellular, and functional heterogeneity of zebrafish intracardiac nervous system.” Nature Communications, 2024. DOI: https://doi.org/10.1038/s41467-024-54830-w
About the Authors
Dr. Caghan Kizil is a neuroscientist specializing in brain regeneration and neurodegenerative diseases. Currently based at Columbia University, his research focuses on understanding how the brain repairs itself and how these mechanisms can be applied to human neurological disorders like Alzheimer’s. Using zebrafish as a model, he has made significant contributions to regenerative neuroscience, exploring how nerve cells regenerate and function in response to injury.
Dr. Konstantinos Ampatzis is a leading researcher in neurobiology at Karolinska Institutet. His work revolves around understanding how the nervous system controls movement and heart function. Through advanced genetic and electrophysiological techniques, he investigates how nerve cells regulate motor functions and cardiovascular processes. His research has provided valuable insights into the role of neural circuits in heart rhythm and movement disorders.
Together, Dr. Kizil and Dr. Ampatzis are pioneering research into the intricate relationship between the nervous system and vital organ functions, opening new possibilities for medical advancements.
