Nearly 40 percent of people will experience syncope or fainting spells at least once in their lifetime, and this brief loss of consciousness, whether caused by pain, fear, heat, hyperventilation, or something else, accounts for the vast majority of hospital emergency room visits; however, researchers are largely unsure of the exact mechanism that causes people to "syncope. However, the exact root mechanism of people's "fainting" is largely unknown to researchers. Recently, a study published in the international journal Nature entitled "Vagal sensory neurons mediate the Bezold-Jarisch reflex and induce syncope. Scientists from the University of California and other institutions have identified, for the first time, a specific genetic pathway between the heart and the brain that is involved in syncope.
One of the researchers' unique approaches is to consider the heart as a sensory organ, rather than the long-held view that the brain sends signals and the heart simply follows instructions. In this study, the researchers used a variety of methods to better understand the specific neural connections between the heart and the brain. We found that the heart also sends signals to the brain that alter brain function, and the information derived from this study may be relevant to better understanding and treating a wide range of psychiatric and neurological disorders related to the brain-heart connection," said researcher Vineet Augustine. Our study provides the first comprehensive elucidation of the genetically defined cardiac reflex, which faithfully encapsulates human syncope, at the physiological, behavioral and neural network levels.
In the article, the researchers jointly investigated the neural mechanisms associated with the Bezold-Jarisch reflex (BJR), a cardiac reflex first described in 1867; for decades, researchers have hypothesized that the BJR, which is characterized by decreases in heart rate, blood pressure, and respiration, might be associated with organic syncope, but because the neural pathways involved in the reflex are currently unknown, the researchers have lacked the information to prove this idea. The researchers focused on analyzing the genetics behind sensory clusters called nodose ganglia, part of the vagus nerve that carries signals for transmission between the brain and internal organs, including the heart; specifically, vagal sensory neurons (VSNs, vagal sensory neurons) project signals to the brainstem and are thought to be directly related to BJR and syncope, and in the researchers' search for novel neural pathways, they found that VSNs that express the neuropeptide Y receptor Y2 (called NPY2R) are closely associated with the well-known BJR response.
Novel brain-heart link identified.
Image From: Nature (2023). DOI:10.1038/s41586-023-06680-7
The researchers then studied this pathway in mice, and they were surprised to find that when NPY2R VSNs were actively set off using optogenetics, a method of stimulating and controlling neurons, the mice, which were able to move freely, immediately fainted. During these events, the researchers recorded data from thousands of neurons in the mice's brains, as well as changes in their heart activity and facial features, including pupil diameter and blinking. Using machine learning in a variety of ways to analyze the data and identify features of interest, the researchers found that once the NPY2R neurons were activated, the mice exhibited rapid pupil dilation and the "rolling of the eyes" that is typical of syncope in humans, while the body's heart rate, blood pressure, and respiratory rate were also suppressed. In addition, the researchers measured a decrease in blood flow to the brain.
The researchers concluded that we were surprised when we saw their eyes roll back in time with the rapid decline in brain activity; a few seconds later, their brain activity and movement returned. Further studies showed that BJR and syncope symptoms disappeared when NPY2R VSNs were removed from the mouse organism. Previous findings have suggested that syncope is caused by reduced blood flow to the brain, and this latest study found that this is indeed the case, but the latest research evidence suggests that brain activity itself may play an important role, and thus the study suggests that the activation of neural pathways in the machinery of the novel genetically-identified VSNs is not only related to the BJR, but also, and more importantly, to the whole physiology of the animal organism, some brain networks and even behavior.
Since neuroscientists primarily study the brain and cardiologists primarily study the heart, it has previously been difficult for researchers to sort out such findings, and many of the studies have been conducted separately; according to the researchers, while traditionally neuroscientists believed that the body simply followed the brain, more and more studies today are showing that the organism sends signals to the brain, which then changes its functions . Based on the researchers' latest findings, they will continue to delve deeper to track down the precise conditions behind how vagus sensory neurons are triggered into action. The researchers note that they also hope to analyze more closely the cerebral blood flow and neural circuits of the brain at the onset of syncope in order to better understand this common but mysterious condition. In addition, the researchers hope that this study will serve as a model to help develop targeted therapies for syncope-related disorders.
In summary, the results of this paper shed light on a genetically defined cardiac reflex mechanism that encapsulates key features of syncope occurrence in humans at the physiological, behavioral, and neural network levels.
