Vagal Sensory Neurons Trigger Fainting Reflex
When vagal sensory neurons are artificially activated in mice, the animals appear to “pass out”.
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Fainting, also called syncope, is when a person briefly loses consciousness. A recent study found that syncope events leading to hospitalization can cost healthcare systems up to $2,420 per day and, in most cases, a clear cause for why someone has passed out cannot be determined.
That’s because the molecular mechanisms underpinning a brief loss of consciousness have not yet been determined, though there have been several hypotheses.
A cardioinhibitory reflex known as the Bezold-Jarisch reflex (BJR) was first reported by von Bezold and Hirt in 1867. It encompasses a variety of neurological and cardiovascular processes that contribute to low blood pressure, breathing and heart rate. A number of studies have suggested BJR might mediate syncope, but as the neurological mechanisms involved in BJR hadn’t yet been deciphered, a clear-cut answer was not available.
That is until a collaborative team of scientists led by Vineet Augustine, assistant professor in the School of Biological Sciences at the University of California San Diego (UCSD), got on the case.
To better understand neural connections between the heart and brain, Augustine and colleagues decided to view the heart almost like a sensory organ. They studied a cluster of sensory neurons called the nodose ganglia, which is part of the vagus nerve. Vagal sensory neurons (VSNs) deliver electrical signals from the visceral organs – including the heart – to the brain stem. Augustine and colleagues found that VSNs expressing a specific receptor – neuropeptide Y receptor Y2 (NPY2R) are linked to BJR.
Stimulating vagal sensory neurons triggers “fainting” in mice
Using optogenetics – a method that uses light to activate and control neurons - the researchers stimulated NYP2R VSNs. Suddenly, mice who had been casually roaming around fainted.
“Photostimulation during high-resolution echocardiography and laser Doppler flowmetry with behavioral observation revealed a range of phenotypes reflected in clinical syncope, including reduced cardiac output, cerebral hypoperfusion, pupil dilation and eye-roll,” the researchers explain.
What is laser doppler flowmetry?
A non-invasive technique that measures cerebral flood flow.
They describe this as the “eureka” moment in the study: “We were blown away when we saw how their eyes rolled back around the same time as brain activity rapidly dropped. Then, after a few seconds, brain activity and movement returned.”
Laying the groundwork
When NPY2R VSNs were removed from the mice, the phenotypes vanished.
This research suggests that brain activity might play a crucial role in syncope, in addition to a reduction in brain blood flow. Augustine and colleagues hope to explore various other conditions under which VSNs are triggered.
"In this study, we identified a genetically defined neural pathway at the heart–brain interface that recapitulates many behavioural phenotypes of human syncope," the researchers write. “This study lays the groundwork for genetic, anatomical and functional dissection of other cardiovascular reflex arcs at the heart–brain interface and their influence on mental processes and behavior. Elucidating the neurobiology of the heart is not only a crucial basic scientific endeavor but also offers substantial translational promise for cardiovascular diseases that remain the leading cause of morbidity around the world."
Reference: Lovelace JW, Ma J, Yadav S, et al. Vagal sensory neurons mediate the Bezold–Jarisch reflex and induce syncope. Nature. 2023. doi: 10.1038/s41586-023-06680-7
This article is a rework of a press release issued by The University of California San Diego. Material has been edited for length and content.