The information we perceive from movement travels from the inner ear to areas of the brain called the vestibular nuclei, which play an important role in motion sickness. Researchers from the UAB Institut de Neurociències (INc-UAB) and the University of Washington have now identified in mice which specific neurons transmit the signals that cause this discomfort. The study has been published in the journal Proceedings of the National Academy of Sciences (PNAS).
The research group, coordinated from the INc-UAB, analyzed the cells of the vestibular nuclei of mice subjected to short and repeated rounds of spinning, and demonstrated the importance of neurons that express the VGLUT2 protein in motion sickness symptoms. According to the authors, these neurons are required for rotation-induced effects of motion sickness, such as decreased appetite, lower body temperature, reduced locomotion, and conditioned taste avoidance (aversion to a taste introduced close to the time of spinning).
Researchers found that blocking these neurons by chemogenetics (molecules specially designed to interact with these specific cells) prevents motion sickness in mice subjected to spinning. And also that their activation by means of a beam of light (optogenetics) in still mice reproduces the same symptoms of dizziness as when they are subjected to rotation.
Specifically, they identified a subgroup of VGLUT2 neurons that express the cholecystokinin gene (CCK-neurons) as being responsible for the effects of motion sickness, and that they send signals to an area of the brain called the parabrachial nucleus, responsible for generating unpleasant sensations.
"The mice to which we administer a drug that blocks the CCK-A receptor have less activation of the parabrachial nucleus and have less motion sickness symptoms", explains Elisenda Sanz, INc-UAB researcher and author of the study.
"Common anti-motion sickness drugs target the histaminergic system, causing drowsiness. CCK-A receptor blocking drugs, which are already approved by the American and European Medicines Associations (FDA and EMA) 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", concludes Albert Quintana, INc-UAB researcher and coordinator of the study.
In future studies, researchers want to further define the contribution of these neurons to other types of dizziness to advance in the approval of drugs that block the CCK-A receptor as a new therapy against this discomfort.
Article: Pablo Machuca-Márquez, Laura Sánchez-Benito, Fabien Menardy, Andrea Urpi, Mònica Girona, Emma Puighermanal, Isabella Appiah, Richard D. Palmiter, Elisenda Sanz and Albert Quintana. «Vestibular CCK signaling drives motion sickness–like behavior in mice». October 17, 2023. PNAS. https://doi.org/10.1073/pnas.2304933120
