Vagus nerve stimulation induces brain vascular rhythms linked to later learning performance

New research provides evidence that stimulating the vagus nerve in mice not only improves long-term learning but also triggers rhythmic changes in brain blood flow. The findings, published in iScience, suggest that the benefits of nerve stimulation may rely partly on vascular responses rather than just chemical signaling between brain cells.

The brain and body are engaged in constant communication, largely through the vagus nerve, which acts as a major information highway. As the longest nerve connecting the brain to the body, it runs from the brainstem down through the neck and into the chest and abdomen, regulating automatic processes like heart rate, breathing, and digestion. Electrical stimulation of this nerve is already used as a medical treatment for certain conditions like epilepsy and depression. As outlined in a 2021 review, sending mild electrical pulses to the vagus nerve is thought to help reshape brain circuits and improve recovery.

Typically, scientists have focused on how this stimulation alters the brain’s chemical environment. For instance, research covered by PsyPost in 2025 indicated that a single session of vagus nerve stimulation can lead to massive drops in specific proteins related to cell-to-cell communication in several brain regions. These chemical changes are generally considered the main drivers of learning and memory.

At the same time, learning requires a substantial amount of energy, which is delivered by the brain’s blood vessels. As demonstrated by a study covered by PsyPost in 2026, blood volume and metabolic dynamics closely track different states of brain activity, such as REM sleep. Additionally, a 2017 review explained that brain cells and nearby blood vessels work together to regulate blood flow, matching energy delivery to the metabolic demands of active brain regions. However, the potential role of blood flow changes in how vagus nerve stimulation affects learning has received little attention.

“In our laboratory, we are interested in how neurons, glial cells, blood vessels, metabolism, and body-derived signals work together to shape brain function,” said study author Ko Matsui, a professor of Super-network Brain Physiology at the Graduate School of Life Sciences at Tohoku University. “Vagus nerve stimulation is a powerful way to activate a major body-to-brain pathway, and it is already used clinically, but its effects are usually discussed mainly in terms of neuromodulatory systems.”

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The authors of the new study sought to understand whether the peripheral signals triggered by vagus nerve stimulation might directly influence brain blood vessel activity. “We wondered whether vascular dynamics might also be part of the story,” Matsui added. “Because learning does not end when the training session ends, we delivered VNS immediately after training and asked whether it could influence delayed processes that support long-term learning.”

The research involved a series of experiments using mice. The scientists surgically implanted a custom-made cuff electrode around the left cervical vagus nerve in the animals. This setup allowed them to deliver controlled electrical pulses while the mice moved freely. To ensure the stimulation was working, the researchers monitored the animals’ pupils and heart rates, as effective vagus nerve stimulation reliably causes the pupils to dilate and the heart rate to drop.

To test learning, the team used a motor training task called the horizontal optokinetic response. In this task, head-fixed mice watched horizontally oscillating vertical stripes on screens. Over time, mice naturally learn to track these moving stripes more accurately with their eyes. The mice underwent four 15-minute training sessions in a single day, spaced one hour apart. Immediately after each session, some mice received vagus nerve stimulation at varying intensities, while a control group received no stimulation.

The researchers tested the mice’s eye-tracking performance again on the second and fifth days to measure long-term learning. They found that vagus nerve stimulation delivered after training selectively enhanced long-term performance. On the first day, the mice that received stimulation learned at the same rate as the control mice, but by the second and fifth days, the mice that received the stimulation demonstrated better eye-tracking performance.

The intensity of the electrical pulses influenced the timing of the benefits. Mice receiving higher-intensity pulses showed improved eye-tracking as early as the second day, while mice receiving lower-intensity pulses showed similar improvements by the fifth day.

“Another surprising aspect was the timing of the behavioral effect,” Matsui said. “VNS did not immediately improve performance during training, but the enhancement emerged later, across days. This delayed effect is consistent with the idea that VNS may influence post-training processes related to long-term plasticity or memory consolidation.”

To observe what was happening inside the brain, the team used a technique called fiber photometry to measure blood volume in the cerebellar flocculus, a brain region involved in this specific type of eye-movement learning. An optical fiber was implanted in the brain to track natural fluorescence in the tissue, which dips when blood vessels expand. The researchers also injected a fluorescent protein into the animals’ bloodstreams to directly visualize blood volume changes.

The measurements showed that each burst of vagus nerve stimulation caused an immediate, two-part reaction in the blood vessels, starting with a brief constriction followed by a larger dilation. Because the stimulation was delivered repeatedly over a 20-minute period following the training task, these reactions created rhythmic fluctuations in local blood volume.

“We expected that VNS might affect brain function through arousal or neuromodulatory pathways, but the rhythmic vascular response in the cerebellar flocculus was striking,” Matsui said. “It suggested that VNS can strongly influence local vascular dynamics in a brain region involved in learning.”

The researchers observed that the mice displaying the largest vascular fluctuations also tended to show the greatest improvements in eye-tracking performance on the fifth day. However, readers should avoid assuming that the changes in blood flow directly caused the improved memory.

“Importantly, the study does not claim that vascular oscillations directly caused the learning enhancement,” Matsui said. “We also did not directly measure ATP, lactate, pyruvate, or oxygen metabolism in this paper.”

“This was a mouse study using invasive cervical VNS, so the findings should not be directly generalized to humans or to non-invasive consumer stimulation devices,” Matsui cautioned. “This does not mean that people can simply stimulate the vagus nerve to become smarter. However, it suggests that signals from the body can influence the brain environment in ways that may be linked to long-term plasticity and learning.”

Future studies will need to manipulate blood vessel activity directly to see if blocking or forcing these fluctuations alters how well the mice learn. Testing different stimulation times could also help clarify exactly how the vagus nerve interacts with the brain’s energy supply networks to support long-lasting memory.

“Our next goal is to directly monitor metabolic signals during VNS, sleep, and learning,” Matsui said. “We are especially interested in how ATP, lactate, pyruvate, oxygen, and vascular dynamics interact during periods when the brain becomes more or less permissive for plasticity.”

“In the long term, we hope to understand whether the brain’s capacity for learning is determined not only by neuronal firing and synaptic activity, but also by the dynamic support provided by glial cells, blood vessels, metabolism, and signals from the body,” he added.

“Together, the REM sleep study and the VNS study point to a broader idea: brain function is embedded in a changing vascular and metabolic environment,” Matsui concluded. “We hope that this perspective will help expand how we think about learning, memory, sleep, and brain-body communication.”

The study, “Vagal nerve stimulation induces vascular oscillations and enhances long-term learning,” was authored by Junyu U. Chen, Yoko Ikoma, and Ko Matsui.