Peripherally Located Type I Vestibular Hair Cells Are Required for Several Motor Behaviors and Stimulus-Evoked Brainstem Neural Responses in Adult Mice

Abstract

The mammalian vestibular system has two types of sensory receptors (hair cells), type I and type II. Understanding the roles of type I and II hair cells in the vestibular system's control of motor behaviors is difficult because most primary vestibular neurons receive inputs from both hair cell types. To test if type I hair cells are required for motor behaviors, we ablated them from peripheral zones of vestibular epithelia in young adult (3–6 months) Fbxo2 CreERT2 ::Rosa26 DTA (experimental) mice of both sexes and then examined motor behaviors and brainstem neuronal responses. Over 90% of peripheral type I hair cells were ablated from vestibular organs by 1 week post-tamoxifen, while central type I and all type II hair cell numbers did not change significantly out to 8 weeks post-tamoxifen. Right after ablation, mice displayed no obvious locomotor abnormalities. However, they could only balance on a rotarod or beam for a few seconds, and gains of the horizontal vestibulo-ocular reflex were reduced by 50%. Deficits persisted to 8 weeks post-tamoxifen, with one exception: 3–6-month-old mice showed partial recovery of rotarod performance after 4 weeks post-tamoxifen, likely due to adaptive motor strategies. Remarkably, 16-month-old mice with type I hair cell ablation failed to recover rotarod function. Motion-induced CFOS expression in vestibular brainstem neurons was nearly eliminated after hair cell ablation, suggesting inputs from vestibular organs had changed significantly. This study demonstrates that peripheral type I hair cells are essential for a vestibular reflex and for some tasks requiring balance and motor coordination.