Why People Faint

“Beware of fainting-fits… though at the time they may be refreshing and agreeable, yet believe me: they will, in the end, if too often repeated and at improper seasons, prove destructive to your constitution.” —Jane Austen, Love and Friendship

From being overwhelmed to overheating to encountering a particularly menacing needle, approximately 40 percent of the population has had the awkward experience of fainting at least once. Yet the precise mechanisms behind these brief moments of unconsciousness, scientifically termed syncope, have in large part remained a mystery.

Oh, gasp.

People faint for various reasons, whether due to heat, hunger, standing for prolonged periods, or even the sight of blood. Gender differences in fainting susceptibility can be attributed to hormonal fluctuations, lower blood volume, orthostatic intolerance, heightened vagus nerve sensitivity, and vasodilation. But fainting vulnerability varies among individuals and isn't solely tied to gender, with other factors like age, overall health, and individual variations also contributing to the phenomenon.

A groundbreaking new study (Lovelace, J. W et al., 2023) has uncovered a neural pathway in mice that appears crucial for controlling fainting. Connecting the heart to the brainstem, this pathway includes sensory neurons that, when activated, induce rapid loss of consciousness, mimicking symptoms observed during human syncope. This discovery challenges the belief that fainting solely results from reduced blood flow to the brain.

Published in Nature on November 1 by Vineet Augustine of the University of California, San Diego, and colleagues, the study introduces a neural pathway associated with sensory neurons operating at the heart-brainstem nexus, offering a deeper understanding of fainting and highlighting dedicated brain circuits manipulating blood-flow reduction. The finding could pave the way for innovative treatment approaches for cardiac-related causes of syncope, as has been noted by Kalyanam Shivkumar, a cardiologist at the University of California, Los Angeles.

The Study's Novel Approach

Understanding fainting's mechanisms has been complex, as researchers typically isolated heart and brain studies. Yet this study's authors developed innovative tools to explore the intricate interaction between these two systems.

By utilizing single-cell RNA sequencing analysis of the nodose ganglion, a component of the vagus nerve that connects the brain to organs including the heart, the researchers identified sensory neurons expressing specific receptors related to the contraction of small blood vessel muscles. These unique neurons, known as NPY2R VSNs, are distinct from other branches of the vagus nerve and establish connections in the muscular regions of the heart, specifically the ventricles, and link to a specific area of the brainstem referred to as the area postrema.

High-resolution ultrasound imaging and optogenetics, a technique for controlling neuronal activity using light, were employed to activate the NPY2R VSNs in mice while simultaneously monitoring various physiological parameters. This real-time manipulation allowed researchers to observe rapid fainting in mice, coupled with symptoms analogous to human syncope, such as reduced heart rate, blood pressure, breathing rate, and brain blood flow. "This was not possible before because you needed to figure out the identity of these neurons," Augustine reported.

Human neurons require oxygen and sugar to function optimally. Depriving them of these vital elements for 2-5 minutes could lead to cell death. However, syncope episodes usually last less than a minute. As Jan Gert van Dijk, a clinical neurologist at Leiden University Medical Centre in the Netherlands, explains, "If you add oxygen again, they'll simply resume their work and do so just as quickly."

To delve deeper into the brain's activity during syncope, the researchers utilized electrodes to record the behavior of thousands of neurons in mice brains as they fainted. The results showcased decreased activity in most brain regions—except for one specific region of the hypothalamus known as the periventricular zone (PVZ).

Blocking the PVZ's activity led to prolonged fainting episodes in mice, while stimulating it caused the animals to awaken and resume their normal activities. This observation underscores the role of a coordinated neural network, which includes NPY2R VSNs and the PVZ, in regulating fainting and recovery.

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Exciting Implications

This discovery offers promise and has generated excitement among clinical professionals and researchers. Richard Sutton, a clinical cardiologist at Imperial College London, notes the thrill of merging the realms of cardiology and neuroscience to explore how the nervous system governs the heart. However, one significant question remains unanswered: What triggers these neurons? Van Dijk describes this as "one of the biggest riddles" of his career.

The new study has unraveled the neural pathway responsible for fainting, potentially opening doors to innovative treatments and a deeper understanding of human physiology. The interconnectedness of the heart and the brain in fainting episodes could lead to improved medical interventions. As researchers explore these findings, the future promises more insights into syncope mechanisms, enhancing our understanding of our remarkable bodies.

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