The impact of peripheral injury on central vestibular pathways

The vestibular system is crucial for postural control and the perception of head and body movement in space. Older adults and those with neurodegenerative disease often are affected disproportionately by cognitive decline and poor vestibular function. These groups are also at risk for increased falls and early death. In the US, these populations are predicted to nearly triple to

~14 million by 2060. Symptoms of vestibular dysfunction, such as dizziness, vertigo, and postural instability, can arise from damage to the vestibular system's peripheral or central components. Studies suggest that loud noise can produce vestibular nerve hypofunction, manifesting as a reduction in the amplitude of P1 of vestibular short latency evoked potentials (VsEPs). Using this

model, morphological and functional changes have been identified in peripheral vestibular organs. However, the role of the brain in noise-induced bilateral vestibular nerve dysfunction is not well understood. Knowledge of underlying mechanisms related to this relationship is necessary for addressing the predicted significant increase in "fall risk" populations and is vital for preventing

their premature deaths. Therefore, we will assess in vivo changes in central neuronal activation (MEMRI and c-Fos), changes in molecular indicators of synaptic transmission at central afferent synapses (CaBPs, vGluTs, and CaVs), and motor function (i.e., skilled walking) in response to vestibular nerve hypofunction generated by noise exposure. Evaluating the contributions of

irregular fibers to neuronal activation in the vestibular nuclear complex and cerebellum and determining how these contributions change over time after noise-induced vestibular nerve hypofunction will ultimately provide both a treatment window and targets for intervention.