Vagus Nerve Stimulation Improves Perceptual Learning in Mice

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Vagus nerve stimulation (VNS) enhances perceptual learning in mice, improving their ability to interpret hearing, vision and other senses with practice, according to researchers from NYU Langone Health. The findings, published in Nature Neuroscience, indicate VNS boosts neuroplasticity in the auditory cortex and activates the cholinergic basal forebrain.

Vagus nerve stimulation can treat various health conditions

The vagus nerve is one of the longest nerves in the human body. Stretching from the brainstem down through the neck and chest to the abdomen, it is an important player in the autonomic nervous system. The vagus nerve controls involuntary body functions such as heart rate, digestion and respiratory rate, and allows communication from the brain to major organs.

The vagus nerve has also been identified as a modulator of the gut–brain axis, transmitting signals about the state of the gut – including information about inflammation, gut bacteria and digestion – directly to the brain. This connection helps regulate mood and emotions.

VNS is a medical technique that involves delivering electrical impulses to the vagus nerve to modulate its activity. Originally developed to treat epilepsy, VNS has since shown promise in managing various conditions like depression, chronic inflammation and migraines. Recently, studies have highlighted the potential of using VNS for treating hearing loss; however, little is known about the internal mechanisms that lead to improved hearing.

VNS improved auditory training

To assess perceptual learning, the team trained 38 mice to be able to tell musical tones apart. The mice were split into 2 groups, and 17 were implanted with a vagus nerve cuff that stimulated the vagus nerve.

 

Initially, all test animals improved over time and made fewer mistakes; however, as the study progressed, the mice who did not receive VNS stopped improving after around a week of training. In contrast, the VNS treatment group continued to get better at the task and made roughly 10% fewer mistakes for most tests than they did before simulation. Mice in this group also made half as many errors as the control group on the most challenging tests, where they had to distinguish between very similar tones.

 

Using two-photon imaging, the team discovered that VNS boosted activity in the cholinergic basal forebrain, a region involved in attention and memory. Activation of cholinergic neurons enhanced task performance, whereas suppressing this area during nerve activation prevented the mice from gaining any additional learning benefits.

 

VNS also increased neuroplasticity in the auditory cortex – a process that enables brain cells to better adapt to new experiences and create memories. This could potentially result in long-term cellular changes that occur well after training.

Improving cochlear implants

Using VNS to boost hearing has previously caused controversy among experts, due to past studies revealing contradictory results. The method also took longer to work than expected; however, the authors note the delay may be due to the electrical pulses distracting the test animals, which may need time to adjust to the sensation.

 

“Our findings suggest that activating the vagus nerve during training can push past the limits of what animals, and perhaps even humans, can learn to perceive,” said lead author Kathleen Martin, a graduate student at the neuroscience institute at NYU Grossman School of Medicine.

 

Martin and the team believe these results have the potential to improve hearing in applications beyond improving one’s musical ability.

 

“These results highlight the potential of vagus nerve stimulation to speed up hearing improvements from cochlear implants. By boosting perceptual learning, this method might make it easier for implant recipients to communicate with others, hear cars approaching and engage more effectively with the world around them,” said senior author Dr. Robert C. Froemke, a professor in the department of otolaryngology – head and neck surgery at NYU Grossman School of Medicine.

 

The team plans to test whether VNS can improve the function of cochlear implants in rodents. Since the vagus nerve is much larger and more complex in humans, further testing is required to know whether their results will be applicable in humans.

 

Reference: Martin KA, Papadoyannis ES, Schiavo JK, et al. Vagus nerve stimulation recruits the central cholinergic system to enhance perceptual learning. Nat Neurosci. 2024. doi: 10.1038/s41593-024-01767-4

This article is a rework of a press release issued by NYU Langone Health. Material has been edited for length and content.