These mysterious neurons in your heart save you from fainting every time you stand

Researchers pinpointed the purpose of mysterious heart neurons in mice—and humans have them, too

By Jacek Krywko edited by Sarah Lewin Frasier

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When you get up out of a chair, your blood pressure instantly increases to compensate for the movement and keep you from fainting. For decades researchers thought neurons called baroreceptors in arteries controlled this process by signaling the sudden drop in blood pressure to the brain, which then issues orders to constrict blood vessels. Some experts suspected that other neurons might help maintain blood pressure during such shifts in posture, but they didn’t know which ones.

For a study published recently in Nature, scientists took a close look at mysterious neurons in the heart that could be involved. “They have been known to exist, but we had no idea what they were sensing,” says study senior author Stephen Liberles, a molecular neuroscientist at Harvard University. Working with mice, his team focused on a protein called PIEZO2 that converts pressure on cell membranes into nerve signals. The researchers found PIEZO2-expressing neurons wrapping around all four chambers of the mouse heart in intricate, weblike structures. “There are such neurons in the human heart as well,” Liberles says.

To understand the neurons’ function, Liberles and his colleagues rotated mice from horizontal to upright while monitoring their vitals in real time. A healthy mouse instantly adjusts its heart rate to compensate for such a posture change. When the researchers injected mice with a toxin that selectively killed the PIEZO2 neurons in the heart, however, their blood pressure plummeted, and they failed to recover. When the researchers induced hemorrhaging in the mice, the PIEZO2 neurons acted long before sensors in the arteries would have been able to sound the alarm—suggesting that they have a direct line on blood volume.

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The team suspects that the brain most likely gets a general sense of blood pressure from the arteries but relies on these newly discovered heart sensors for high-fidelity updates on the volume of blood moving through the organ.

“The authors conclude that PIEZO2-expressing neurons are required to maintain blood pressure and support survival during blood-volume depletion,” says Ardem Patapoutian, a molecular biologist at the Scripps Research Institute, who was not involved in the study. Patapoutian won the 2021 Nobel Prize in Physiology or Medicine for discovering the role PIEZO1 and PIEZO2 proteins play in sensing mechanical stimuli. “This is an important study that offers valuable insights into cardiovascular regulation,” he adds. But our hunt for mysterious circulatory neurons is far from over.

Liberles and his colleagues note in their study that there are at least six different neuron types in the cardiovascular system, and we still don’t know the function of three of those six. “We want to know how they work,” Liberles says. “There’s a lot to do.”