Vagus Nerve Neurons Isolated and Recorded for the First Time

In 2020, Professor Vaughan Macefield’s team at Monash University achieved a world-first by recording signals from the human vagus nerve in vivo. Previously, direct recordings could only be obtained from laboratory animals. .

The research, published in The Journal of Physiology, would open “exciting new opportunities” for studying the physiology of the nerve in human health and disease, the authors predicted.

Indeed, the vagus nerve has been the focal point of much research over the last four years, leading to a broader understanding of its role beyond “rest and digest” functions. Studies have shed light on the nerve’s contribution to exercise, gut microbiome modulation, infection response and even higher-order cognitive functions such as goal-directed behavior.

Now, Macefield – who leads the Human Neurophysiology Lab in the Department of Neuroscience at Monash University – and colleagues have achieved yet another milestone. In The Journal of Physiology, they share their work isolating activity from individual neurons within the vagus nerve.

“We have managed to isolate the activity of individual vagal neurons and identified those that are responsible for either informing the brain about cardiovascular function (afferent neurons) or controlling the rate of the heart beat (efferent neurons),” Dr. David Farmer, the study’s first author and a research fellow in the Department of Neuroscience, said.

The vagus nerve under focus

The vagus nerve is the 10^th cranial nerve. It’s neurons connect our brains with multiple organs throughout the body – hence it’s nickname as “the wanderer”. In a press release, Farmer emphasized that human studies were necessary to progress research from the animal studies that provided great insight into the brain’s control over cardiovascular function.

Macefield and colleagues took recordings from the right or left cervical vagus nerve in 15 healthy participants, aged 19–59 years, using tungsten microelectrodes and ultrasound guidance.

The cervical portion of the vagus nerve comprises nerve fibers that innervate the heart, lungs and the abdomen. “The penetration of different vagal fascicles was accomplished by slight manual adjustments of the recording microelectrode, following which the ultrasound probe was removed,” the researchers explained.

After obtaining baseline records, participants were asked to engage in slow deep breathing exercises – five seconds inhaling, followed by five seconds exhaling. “This manoeuvre was used to identify vagal recording sites with activity that showed respiratory modulation, as such modulation is a characteristic of vagal fascicles that contain neurons with respiratory or cardiovascular function,” Macefield and colleagues described. “Additionally, this manoeuvre likely maximises the activity of cardioinhibitory neurons, thus increasing the likelihood of their being observed in the current study.”

Next, the microelectrode was moved to another site, where the process was repeated. Template-based spike sorting was used to isolate the activity of individual neurons.

Firing patterns aid functional identification

Collectively, the activity of 44 cardiac rhythmic neurons was isolated, including 22 myelinated axons, and 22 unmyelinated axons. “By consideration of each unit's firing pattern with respect to the cardiac and respiratory cycles, the functional identification of each unit was attempted,” the researchers said.

“Positive-going spikes (indicative of myelinated axons) whose firing displayed cardiac and post-inspiratory or expiratory rhythmicity were classified as putative cardioinhibitory efferent neurons,” they continued. “Negative-going spikes (indicative of unmyelinated axons) that showed cardiac and post-inspiratory or expiratory rhythmicity were classified as putative cardiac-projecting efferent neurons.”

While this study was conducted in healthy individuals, the researchers have set their sights on repeating their method in patients with cardiovascular disease. “In cardiovascular disease states, the activity of vagal neurons that slow the heart appears to be reduced,” Farmer said. “Additionally, activation of the neurons that monitor heart function produce altered cardiovascular reflexes.”

“We don’t know precisely why that is or what neurons are responsible. The ability to isolate the activity of these neurons from vagal recordings in human participants may enable us to work this out, which is pretty cool,” he concluded.

Reference: Farmer DGS, Patros M, Ottaviani MM, et al. Firing properties of single axons with cardiac rhythmicity in the human cervical vagus nerve. J Physiol. 2024;n/a(n/a). doi: 10.1113/JP286423

This article is a rework of a press release issued by Monash University. Material has been edited for length and content.