Physiology of Vestibular Compensation

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DESCRIPTION (provided by applicant): Disruption of vestibular signals from one labyrinth results in asymmetries in the angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration head movements. Studies during the previous funding period have elucidated linear and nonlinear components of the angular VOR in the squirrel monkey, demonstrated selective adaptation of these components with magnifying or minimizing spectacles, compared the horizontal angular VOR in squirrel monkeys and macaques in response to rapid rotations, defined the response properties of vestibular-nerve afferents to rapid head rotations, and analyzed changes in the angular VOR, afferents, and hair cells following unilateral ototoxic vestibular injury with gentamicin. The proposed research builds upon previous accomplishments through studies that are organized into three specific aims. The experiments are performed in chinchillas and in macaques. Studies in Aim I will define the responses of vestibular-nerve afferents to steps of acceleration and study the contributions of irregularly discharging afferents to the horizontal VOR evoked by these rapid head rotations. Bilateral, anodal galvanic currents delivered to each labyrinth will be used to substantially attenuate or silence irregular afferents during rapid head rotations. The experiments that are conducted in macaques will involve analysis of the normal VOR as well as following spectacle-induced adaptation. Aim II will investigate the contribution to VOR compensation of preserved resting rate in afferents on the side of a unilateral vestibular lesion and of afferents from the contralesional (intact) labyrinth. The unilateral lesion that preserves resting rate but abolishes or markedly attenuates responses to motion involves intratympanic injection of gentamicin. Aim III will examine neural correlates of compensatory changes in the horizontal VOR in macaques after unilateral labyrinthectomy. These experiments will determine if the discharge properties of vestibular-nerve afferents on the contralateral side change following unilateral labyrinthectomy. The dynamics of vestibular nuclei neurons that mediate the VOR will be studied following unilateral labyrinthectomy. The role of proprioceptive inputs and anticipatory mechanisms in modifying the responses of these central neurons will be determined by comparing neuronal responses during actively and passively generated head-on-body and whole-body rotations.