We just published a paper in PNAS in which we describe in mice which specific neurons transmit the signals that cause this discomfort.
In this article, which is a collaboration with the University of Washington, we 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.
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).
Blocking them 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, we identified a subgroup of VGLUT2 neurons that express the cholecystokinin gene (CCK-neurons) as being responsible for the effects of motion sickness by sending 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. 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.
In future studies, we 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://www.pnas.org/doi/10.1073/pnas.2304933120