Aging and Dysfunction in the Peripheral Vestibular System

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Project Summary Vestibular dysfunction becomes more prevalent with age and it is estmated that more than 80% of people over 80 years old experience dysfunction5. Furthermore, approximately 8 million adults in the US suffer from balance impairment due to damage to the peripheral vestibular system, but effective treatments for balance dysfunction are virtually non-existent. Vestibular hair cells within vestibular canal and otolith organs convert hair bundle motion into receptor potentials and sensory information is relayed to the brain by action potentials in vestibular afferent nerves. Afferents in central zones of vestibular neuroepithelia exhibit different responses to vestibular stimuli than afferents in peripheral zones. There are three types of vestibular afferents: calyx-only afferents innervate one or more type I hair cells, bouton dendrites innervate type II hair cells and dimorphic afferents contact both hair cell types. Calyx-only afferents are present only in central zones and have irregular firing patterns, whereas dimorphic afferents exist in both zones and have regular firing patterns. We will study age-related dysfunction in calyx-bearing afferents in gerbil vestibular organs using novel preparations developed in the laboratories of the principal investigators. We will use electrophysiological, hair bundle stimulation, immunohistochemical and behavioral approaches to address age-related changes in mature and aged vestibular epithelia. In Aim 1 we will determine if functional changes in vestibular hair cell mechanotransduction and/or basolateral currents occur with age. Aim 2 will test the hypotheses that synaptic degeneration of calyx terminals will manifest as morphological uncoupling of type I hair cells from their associated calyces and deficits in vestibular evoked responses and behaviors. In Aim 3 we will directly investigate changes at the type I hair cell/calyx synapse by recording spontaneous activity and responses to hair bundle stimulation in mature and aged calyx afferents. Our investigative team is uniquely positioned to carry out the proposed studies. Results from this work will provide new information on how the aging process impacts peripheral vestibular signals and may inform development of vestibular neurotherapeutics targeting afferent nerves in order to restore normal vestibular function.