The mammalian efferent vestibular system plays a crucial role in the high-frequency response and short-term adaptation of the vestibuloocular reflex

Although anatomically well described, the functional role of the mammalian efferent vestibular system (EVS) remains unclear. Unlike in fish and reptiles, the mammalian EVS does not seem to play a role in modulation of primary afferent activity in anticipation of active head movements. However, it could play a role in modulating long-term mechanisms requiring plasticity such as vestibular adaptation. We measured the efficacy of vestibuloocular reflex (VOR) adaptation in alpha 9-knockout mice. These mice carry a missense mutation of the gene encoding the alpha 9 nicotinic acetylcholine receptor (nAChR) subunit. The alpha 9 nAChR subunit is expressed in the vestibular and auditory periphery, and its loss of function could compromise peripheral input from the predominantly cholinergic EVS. We measured the VOR gain (eye velocity/head velocity) in 26 alpha 9-knockout mice and 27 cba129 control mice. Mice were randomly assigned to one of three groups: gain-increase adaptation (1.5x), gain-decrease adaptation (0.5x), or no adaptation (baseline, 1x). After adaptation training (horizontal rotations at 0.5 Hz with peak velocity 20 degrees/s), we measured the sinusoidal (0.2-10 Hz, 20-100 degrees/s) and transient (1,500-6,000 degrees/s(2)) VOR in complete darkness. alpha 9-Knockout mice had significantly lower baseline gains compared with control mice. This difference increased with stimulus frequency (similar to 5% <1 Hz to similar to 25% >1 Hz). Moreover, vestibular adaptation (difference in VOR gain of gain-increase and gain-decrease adaptation groups as % of gain increase) was significantly reduced in alpha 9-knockout mice (17%) compared with control mice (53%), a reduction of similar to 70%. Our results show that the loss of alpha 9 nAChRs moderately affects the VOR but severely affects VOR adaptation, suggesting that the EVS plays a crucial role in vestibular plasticity.