Control of Spatial Orientation of the Angular Vestibulo‐Ocular Reflex by the Nodulus and Uvula of the Vestibulocerebellum

Abstract: Eye velocity produced by the angular vestibulo‐ocular reflex (aVOR) tends to align with the summed vector of gravity and other linear accelerations [gravito‐inertial acceleration (GIA)]. Defined as “spatial orientation of the aVOR,” we propose that it is controlled by the nodulus and uvula of the vestibulocerebellum. Here, electrical stimulation, injections of the GABAA agonist, muscimol, and single‐cell recordings were utilized to investigate this spatial orientation. Stimulation, injection, and recording sites in the nodulus were determined in vivo by MRI and verified in histological sections. MRI proved to be a sensitive, reliable way to localize electrode placements. Electrical stimulation at sites in the nodulus and sublobule d of the uvula produced nystagmus whose slow‐phase eye‐velocity vectors were either head centric or spatially invariant. When head centric, the eye velocity vector remained within ±45° of the vector obtained with the animal upright, regardless of head position with respect to gravity. When spatially oriented, the vector remained relatively constant in space in one on‐side position, with respect to the vector determined with the animal upright. A majority of induced movements from the nodulus were spatially oriented. Spatially oriented movements were generally followed by after‐nystagmus, which had the characteristics of optokinetic after‐nystagmus (OKAN), including orientation to the GIA. After muscimol injections, horizontal‐to‐vertical cross‐coupling was lost or reduced during OKAN in tilted positions. This supports the hypothesis that the nodulus mediates yaw‐to‐vertical or roll cross‐coupling. The injections also shortened the yaw‐axis time constant and produced contralateral horizontal spontaneous nystagmus, whose velocity varied as a function of head position with regard to gravity. Nodulus units were tested with static head tilt, sinusoidal oscillation around a spatial horizontal axis with the head in different orientations relative to the pitching plane, and off‐vertical axis rotation (OVAR). The direction of the response vectors of the otolith‐recipient units in the nodulus, determined from static and/or dynamic head tilts, were confirmed by OVAR. These vector directions lay close to the planes of the vertical canals in 7/10 units; many units also had convergent input from the vertical canals. It is postulated that the orientation properties of the aVOR result from a transfer of otolith input regarding head tilt along canal planes to canal‐related zones of the nodulus. In turn, Purkinje cells in these zones project to vestibular nuclei neurons to control eye velocity around axes normal to these same canal planes.