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Vagus nerve is linked to brain activity — Electrical Stimulation Improves Depression in Mice: Findings from Tohoku University and the University of Tokyo


The research group of Professor Takuya Sasaki of the Graduate School of Pharmaceutical Sciences at Tohoku University and Professor Yuji Ikegaya of the Graduate School of Pharmaceutical Sciences at the University of Tokyo has discovered that the vagus nerve, which conveys information on internal organs to the brain, is involved in the formation of normal emotions in conjunction with brain wave patterns in the prefrontal cortex and amygdala. They have simultaneously analyzed the physiological signals from the vagus nerve, as well as the brain's prefrontal cortex and amygdala in mice, which are important regions associated with emotions. In healthy mice, the strength and weakness of brain wave patterns were linked to vagus nerve activity; however, this correlation was not observed in depressed mice. They further confirmed that electrical stimulation of the vagus nerve could reverse this depressive state. The results are expected to lead to elucidation of the mechanisms of mental disorders and the development of treatment and were published in the international academic journal Nature Communications.

Overview of the Research Findings
In healthy mice, the prefrontal cortex generates 20-30 Hz oscillations correlated with vagus nerve activity (left). These mice can maintain a quiet behavioral state in anxiety-related environments. Mice exhibiting depressive-like symptoms after psychological stress showed weakened cooperation between the vagus nerve and prefrontal activity, leading to an inability to maintain a quiet state (right). Chronic electrical stimulation of the vagus nerve in such depressive-like mice could restore the prefrontal-vagal physiological activity and a behavioral state similar to that of healthy mice (blue arrow, left).
Provided by Tohoku University

Although emotions have been traditionally believed to originate only in the brain, recent research has shown that they are also influenced by the state of various internal organs. For example, a person is more likely to be depressed when the intestinal environment deteriorates. The vagus nerve, which runs throughout the body, serves as a pathway to transmit information from these organs to the brain. Nevertheless, it remained unclear what type of neural activity is produced by vagus nerve and how the nerve affects brain activity and emotions.

The research group analyzed these relationships by simultaneously measuring physiological signals from the prefrontal cortex and amygdala, which are related to the vagus nerve and emotions, using mice, which have a vagus nerve structure similar to that in humans. An apparatus was devised to measure the electrical activity of vagus nerve in resting mice by placing a cuff-type electrode on the vagus nerve in the neck of the mice. They confirmed that vagus nerve activity was attenuated when mice were subjected to chronic mental stress such as being attacked and defeated by other mice. They further searched for the brain region linked to the vagus nerve and found that the linked region is the prefrontal cortex. Although the prefrontal cortex has long been suggested to be involved, this research is the first to clearly show its participation.

Metal electrodes were implanted in the amygdala, which has been speculated to be involved in emotion along with the prefrontal cortex, and the brain activity (brain wave patterns) in this area was investigated simultaneously with vagus nerve activity. In healthy mice, it was found that the increase/decrease in vagus nerve activity correlated with the magnitude of brain waves in the 20-30 Hz band in the prefrontal cortex and amygdala. The dynamic changes in vagus nerve and brain waves in an environment where anxiety fluctuates were investigated in normal mice and depressed (depression-like) mice during an elevated plus maze test, and brain waves in the same frequency band as the active vagus nerve were examined.

A link between brain waves and the vagus nerve was observed in healthy mice, whereas the link was significantly weakened in depressed mice. In healthy mice, vagus nerve activity significantly changes in open spaces or when they were moving around, but these changes were not observed in depressed mice. Based on these results, they examined whether activating the vagus nerve in depressed mice would bring the mental state and brain activity of depressed mice closer to normal.

Chronic electrical stimulation of the vagus nerve in depressed mice over 2 weeks normalized the brain wave patterns of the prefrontal cortex in the elevated plus maze, similar to that in healthy mice. Furthermore, the vagus nerve and brain waves were linked, resulting in normal behavior. The recovery from depression caused by the stimulation is expected to continue for several weeks.

Sasaki commented, "It is thought that vagus nerve stimulation may be used in patients with treatment-resistant depression who do not respond to medications. Although transcranial magnetic stimulation has been conventionally used, it is unclear where and how this stimulation method is effective. It is now expected that the mechanism same as the above may be useful for vagus nerve stimulation. Although vagus nerve stimulation was originally invasive, noninvasive techniques are currently available. By looking at the regions of vagus nerve stimulation revealed in this study, we believe that we may be able to suggest appropriate targeting areas for vagus nerve stimulation and indicators of brain activity."

Journal Information
Publication: Nature Communications
Title: Stress-induced vagal activity influences anxiety-relevant prefrontal and amygdala neuronal oscillations in male mice
DOI: 10.1038/s41467-023-44205-y

This article has been translated by JST with permission from The Science News Ltd. ( Unauthorized reproduction of the article and photographs is prohibited.

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