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Scientists from the University of California, San Diego have solved the mystery of syncope by identifying the exact genetic mechanism that connects the heart and brain. This discovery not only sheds light on one of the most common medical phenomena, but also opens the way for the development of effective treatments for conditions in which fainting is common.
Previously, it was thought that the brain sends a signal to the heart, which immediately responds to it. However, a team led by assistant Professor of biological Sciences Vinit Augustin showed that this is only part of the process. "We found that the heart also sends signals back to the brain, which can alter brain function," says Augustine.
The researchers focused on studying the neural mechanisms associated with the Bezold-Jarisch reflex (BJR), a heart function that was identified as early as 1867 and suggested as a cause of syncope, but has not yet been proven. They studied the genetic makeup of a sensory cluster known as the nodal ganglion, part of the vagus nerves that transmit signals between the brain and the heart. It is here that neurons expressing the Y-type 2 neuropeptide receptor (NPY2R) were found to have a significant association with BJR physiology.
Using optogenetics to target specific neurons, the researchers were able to activate NPY2R VSNs in mice, which instantly caused them to faint. Observations, extensive data on neural activity in the brain, and machine learning allowed scientists to show how important NPY2R plays in causing syncope.
In addition, when these neurons were activated, the mice showed dilated pupils and the characteristic "inversion of the eyes" characteristic of syncope, as well as a slowing of the heartbeat, respiration, and a drop in blood pressure. "We were startled to see their eyes roll up at the same time that brain activity plummeted," the researchers report in a summary of the work. "Then, after a few seconds, brain activity and movement returned. It was our eureka moment."
When the researchers eliminated the NPY2R VSNs neurons, the Bezold-Yarisch reflex and subsequent syncope were no longer observed in the mice. This discovery highlights that the interaction between the brain and the heart is mutual: not only does the brain control the heart, but the heart also affects brain function. Thus, reduced blood flow to the brain, previously thought to be the main cause of syncope, is now complemented by a new understanding of two-way communication between these two vital organs.
"Traditionally, neuroscientists think that the body just follows the brain, but now it's becoming very clear that the body sends signals to the brain, and then the brain changes its function," says Augustine.
These findings open up potential avenues for research to better understand and treat a range of psychiatric and neurological disorders that have a clear connection between the brain and the heart.
"We also hope to take a closer look at blood flow in the brain and neural pathways in the brain at the moment of syncope to better understand this common but mysterious condition," the researchers note in the study.
The team now hopes to track down the exact conditions needed to trigger VSNs, and use the research to develop targeted therapies for syncope-related health conditions.
The study was published in the journal Nature, and the video below captures the heart-brain "dialogue" as heart activity slows down in response to stimulation of syncope-inducing VSNs.
Scientists from the University of California, San Diego have solved the mystery of syncope by identifying the exact genetic mechanism that connects the heart and brain. This discovery not only sheds light on one of the most common medical phenomena, but also opens the way for the development of effective treatments for conditions in which fainting is common.
Previously, it was thought that the brain sends a signal to the heart, which immediately responds to it. However, a team led by assistant Professor of biological Sciences Vinit Augustin showed that this is only part of the process. "We found that the heart also sends signals back to the brain, which can alter brain function," says Augustine.
The researchers focused on studying the neural mechanisms associated with the Bezold-Jarisch reflex (BJR), a heart function that was identified as early as 1867 and suggested as a cause of syncope, but has not yet been proven. They studied the genetic makeup of a sensory cluster known as the nodal ganglion, part of the vagus nerves that transmit signals between the brain and the heart. It is here that neurons expressing the Y-type 2 neuropeptide receptor (NPY2R) were found to have a significant association with BJR physiology.
Using optogenetics to target specific neurons, the researchers were able to activate NPY2R VSNs in mice, which instantly caused them to faint. Observations, extensive data on neural activity in the brain, and machine learning allowed scientists to show how important NPY2R plays in causing syncope.
In addition, when these neurons were activated, the mice showed dilated pupils and the characteristic "inversion of the eyes" characteristic of syncope, as well as a slowing of the heartbeat, respiration, and a drop in blood pressure. "We were startled to see their eyes roll up at the same time that brain activity plummeted," the researchers report in a summary of the work. "Then, after a few seconds, brain activity and movement returned. It was our eureka moment."
When the researchers eliminated the NPY2R VSNs neurons, the Bezold-Yarisch reflex and subsequent syncope were no longer observed in the mice. This discovery highlights that the interaction between the brain and the heart is mutual: not only does the brain control the heart, but the heart also affects brain function. Thus, reduced blood flow to the brain, previously thought to be the main cause of syncope, is now complemented by a new understanding of two-way communication between these two vital organs.
"Traditionally, neuroscientists think that the body just follows the brain, but now it's becoming very clear that the body sends signals to the brain, and then the brain changes its function," says Augustine.
These findings open up potential avenues for research to better understand and treat a range of psychiatric and neurological disorders that have a clear connection between the brain and the heart.
"We also hope to take a closer look at blood flow in the brain and neural pathways in the brain at the moment of syncope to better understand this common but mysterious condition," the researchers note in the study.
The team now hopes to track down the exact conditions needed to trigger VSNs, and use the research to develop targeted therapies for syncope-related health conditions.
The study was published in the journal Nature, and the video below captures the heart-brain "dialogue" as heart activity slows down in response to stimulation of syncope-inducing VSNs.
