Vagus nerve stimulation enhances perceptual learning in mice, study suggests

Recent neuroscience studies have been investigating how the stimulation of some nerves, particularly the vagus nerve, using electrical pulses affects neural activity in the mammalian brain. The vagus nerve, the longest cranial nerve in the human body, is known to play a key role in the regulation of heart rate, digestion, stress and other physiological processes.

Some findings suggest that stimulating the vagus nerve can enhance the plasticity of the brain, which is its ability to reorganize itself following experiences. This could in turn facilitate perceptual learning, the process by which humans and other animals become better at distinguishing and interpreting different sensory inputs.

Researchers at New York University School of Medicine set out to further examine the effects of vagus nerve stimulation (VNS) on neural activity and perceptual learning in mice. Their findings, published in Nature Neuroscience, suggest that stimulating the vagus nerve enhances the performance of mice on a perceptual learning task by activating the central cholinergic system.

“About 10 years ago, a lot of people here in the US got excited about the potential for VNS to promote neuroplasticity, improving recovery outcomes after neurological damage or even boosting performance in the normal brain,” Robert C. Froemke, co-author of the paper, told Medical Xpress.

“This led to … a big collective effort across many labs, studying VNS and motor learning for skill acquisition and auditory perceptual learning from 2017–2021. We were part of that team working on mice with amazing tools for studying neural circuits, but the vagus nerve in a mouse is very small.”

To conduct their experiments assessing the impact of VNS stimulation on the brain activity and learning of mice, Froemke and his colleagues first had to develop a new tiny electrode and a suitable perceptual learning task. Subsequently, the team formulated a hypothesis about how VNS might enhance sensory perception (i.e., what would become active or change in the brain if it did).

“We trained mice on an auditory task,” explained Froemke. “They had to lick left whenever they heard one sound (tone A) and lick right for any other sound. If the other sounds were very close to tone A, the task was challenging and they could get confused, sort of like at the eye doctor when you have to read smaller and smaller letters on the eye chart.”

As the mice gradually learned to complete the perceptual learning task, the researchers stimulated their vagus nerve using the electrode they developed. Concurrently, they also recorded activity in the animals’ auditory cortex (involved in processing sounds), as well as in the locus coeruleus of the brainstem and the basal forebrain, two regions implicated in attention.

“We found that indeed, VNS could augment training and improve perceptual discrimination beyond the limit achieved by training and effort alone,” said Froemke. “However, it takes a while, a few weeks of daily training and stimulation to see enduring gains at the most challenging difficulty levels. We also identified neural changes supporting this perceptual improvement.”

The evidence gathered by the team at New York University suggests that in mice VNS activates the central cholinergic system, a neural network that utilizes the neurotransmitter acetylcholine to communicate with other neurons and supports various brain functions. The activation of this neural network was found to in turn enhance the performance of mice in the perceptual learning task they developed.

In the future, the recent work by Froemke and his colleagues could help to refine methods for stimulating the vagus nerve, while the experimental task they developed could be used by other researchers to conduct further studies probing the link between VNS and perceptual learning.

In their next studies, the researchers plan to conduct further experiments assessing the potential of VNS for boosting the efficacy of cochlear implants.

“A lot of people with deafness that have cochlear implants struggle to get much use out of the device, even months or years after implantation, and there is currently no treatment for helping restore hearing and improve functionality,” added Froemke.

“We think that in both animals and human users of cochlear implants, we can use VNS to help speed up and enhance the use of these amazing medical devices.”

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