Semicircular Canals Input Can Modify the Fast-Phase Nystagmus in Off-Vertical Axis Rotation of Mice

Vestibular research is essential for understanding and treating disorders such as vertigo and Meniere's disease. The vestibulo-ocular reflex (VOR) is a key method for assessing vestibular function and an essential tool for diagnosing vertigo. Traditionally, the VOR comprises angular VOR (aVOR) and translational VOR (tVOR), which originate from the vestibular semicircular canals (SCCs) and otolith organs, respectively. VOR consists of both fast-phase and slow-phase eye movements, which functionally interact to contribute to gaze control. However, to calculate the gain and phase parameters of the VOR, it is common practice to exclude fast-phase information superimposed on slow-phase eye movements. As a result, the information contained in the fast phase has not been fully utilized. OVAR is primarily used to evaluate otolith function, as there is no SCC input during its steady state. It is widely accepted that fast-phase nystagmus (FPN) during OVAR is generated by periodic otolith inputs via the central vestibular velocity storage mechanism. Surprisingly, we discovered in this study that SCC input can modify the generation of FPN in mouse OVAR test, as demonstrated by testing Zpld1 (Zona pellucida-like domain containing 1 protein) mutant mice with SCC deficits. This finding was further confirmed using both unilateral and bilateral semicircular canals dehiscence surgical models. In addition to revealing the dependence of FPN on SCC input, we demonstrated that FPN can be used to evaluate vestibular function, particularly in conditions that are difficult to assess using slow-phase eye movements, such as unilateral vestibular lesions and central modulation via baclofen treatment.