The Neural Mechanism of Motion Sickness Alleviation by Anticipatory Sound

Abstract Motion sickness (MS) is a common response to conflicting motion signals and can cause nausea, dizziness, malaise, and reduced activity. Sound can lessen MS, but how auditory cues influence the brain circuits that generate these symptoms is unclear. Here we show, using a repeated rotation paradigm in male mice, that a brief anticipatory tone reduces MS-like responses. We identify Cerebellin-2-expressing (Cbln2 + ) glutamatergic neurons in the medial vestibular nuclei (MVN), a brainstem center for balance signals, as key drivers of these responses. These neurons act through two separable outputs: a projection to the ventrolateral periaqueductal gray that promotes MS-like behavior, and a projection to the nucleus of the solitary tract that contributes to nausea-related aversion, likely through the parabrachial nucleus. Anticipatory tone cues recruit an inhibitory pathway from the central amygdala to suppress Cbln2 + MVN neurons. These findings reveal how auditory prediction can dampen vestibular circuits that drive MS.