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, then examined motor behaviors and brainstem neuronal responses. Over 90% of peripheral type I hair cells were ablated from vestibular organs by one 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.Significance Statement This study demonstrates that a specific subpopulation of vestibular sensory receptor cells (peripherally located type I hair cells) is required in adult mice to maintain normal vestibular function, including the vestibulo-ocular reflex, balance and motor coordination, and neuronal responses to a motion stimulus. These findings have implications for the underlying pathology in some types of balance disorders and may inform new strategies to restore vestibular function after hair cell damage or degeneration.