Specific neurons could be the culprits behind the unwelcome feeling of motion sickness. New research has implications for how we could treat this travel inconvenience. Image credit: Denys Argyriou via Unsplash
Motion sickness, or kinetosis, was first described by the Greek physician Hippocrates, who wrote, ‘sailing on the sea proves that motion disorders the body’. It is an unwelcome condition, turning travel into a nauseating ordeal for many. When the eyes perceive a stable environment, such as when reading in a car, but the vestibular system in the inner ear senses motion, the incongruity between the sensory inputs confuses the brain and gives rise to the symptoms of motion sickness, which include nausea, dizziness, and sweating. It is widely accepted that motion sickness arises from conflicts between visual and vestibular sensory inputs and the expected motion and body position information based on past memories. However, the exact neurological underpinnings of this sensation have not yet been fully understood.
A recent study published in Proceedings of the National Academy of Sciences (PNAS) by Albert Quintana and colleagues at the Autonomous University of Barcelona, Spain, claims to have identified the specific cells (neurons) within the brains of mice that cause the sensation of motion sickness. Groups of neurons called the vestibular nuclei (VN) are known to be critical for processing movement from the inner ear. Previous evidence has demonstrated that activating VN neurons through motion reproduced motion sickness-like alterations in rats and mice. These VN neurons were the focus of the recent study by Quintana and colleagues, particularly a subset of neurons that previously were shown to play a role in balance.
In the study, the researchers inhibited a specific group of neurons in the VN. This was done using a technique called chemogenetics, where a chemical molecule is targeted to a specific subpopulation of cells in order to alter cellular activity. It was found that targeted inhibition of these specific VN neurons, called VGLUT2-expressing neurons, prevented both decreased movement and suppressed appetite, which are symptoms seen in mice when motion sickness is induced by spinning the mice in a rotational device. Moreover, by activating these neurons using a technique called optogenetics, where specific groups of neurons can be switched on or off using light, symptoms of motion sickness (similar to those created from physically inducing motion sickness via spinning the mice) were induced. It seems, therefore, that VGLUT2-expressing neurons in the VN are crucial in the development of motion sickness symptoms.
It was found that targeted inhibition of these specific VN neurons, called VGLUT2-expressing neurons, prevented both decreased movement and suppressed appetite, which are symptoms seen in mice when motion sickness is induced by spinning the mice in a rotational device.
The researchers went on to identify the genetic identity of these motion sickness neurons. A subpopulation of neurons investigated were CCK neurons, which had previously been shown to be involved in nauseogenic responses. Activating these CCK neurons using optogenetics also led to a decrease in movement and appetite suppression—key motion sickness symptoms in mice. Also, as author of the study Elisenda Sanz explains, if a drug called devazepide, which blocks CCK signalling, is administered before the mice are spun around, motion sickness symptoms are prevented.
This research could have extremely important implications for treating motion sickness in humans. Although the symptoms are highly conserved across species, some scientists have questioned the validity of using movement and quantity of food eaten as proxy measurements for nausea and the use of rodents to study motion sickness more generally. This is because mice do not have a vomiting reflex, and there is some difficulty in clearly identifying nausea. Nevertheless, mice do reliably display certain behaviours characteristic of motion sickness and can offer a valuable tool for preclinical research into this condition.
This research could have extremely important implications for treating motion sickness in humans.
In most instances, motion sickness is currently managed by behavioural and environmental modifications (such as avoiding travelling). Drug treatments for motion sickness are used for the treatment of more severe cases and for patients who do not respond to more conservative measures. Such medications include anticholinergic agents and antihistamines, which are particularly helpful when given prophylactically (before the onset of motion sickness symptoms). These drugs are limited by their side effects, such as dry eyes and mouth, and drowsiness. As author of the study Albert Quintana concluded, ‘Common anti-motion sickness drugs target the histaminergic system, causing drowsiness. CCK-A receptor blocking drugs, which are already approved…as a treatment for gastric problems, are safe and do not have this unwanted effect, so they would be an excellent option to treat motion sickness’. Future research should further define the contribution of these CCK neurons to other types of dizziness, so that the approval of new drugs can be advanced.
In an age where travel is paramount, a treatment to motion sickness would be warmly welcomed.
In an age where travel is paramount, a treatment to motion sickness would be warmly welcomed. This study provides greater insight into the previously unknown neurobiological underpinnings and regulation of motion sickness. Future studies detailing the behavioural and physiological contribution of other types of neurons will provide a more complete profile of the neurobiology of motion sickness, and any medications developed as a result of this study could ultimately provide relief to many.