This project will expand on the work of my NIDCD K23 Project, "Vestibular Effects of Intratympanic Gentamicin." We have found that human subjects who have intratympanic gentamicin treatment for Meniere's disease have a decline in the angular vestibulo-ocular (AVOR) reflex gain for rapid head rotations that excite the treated labyrinth. Some of these subjects have shown increased gains on the same test at later times, suggesting either recovery of peripheral vestibular function or central augmentation of gain. We have also recorded the responses of vestibular afferents in chinchillas after the identical intratympanic gentamicin treatment. This causes a profound loss of sensitivity to vestibular stimulation, but spontaneous afferent discharge is preserved. This suggests that hair cells may be only partially damaged, such that they can release neuro-transmitter to elicit the baseline activity of afferents but that their apical structures cannot transduce head acceleration. These findings correlate well with recent histologic evidence that mammalian hair cells exposed to gentamicin may shed their apical structures but maintain their basal ones (Zheng et al., 1999). The first goal of this project is to determine if the afferent processes contacting vestibular hair cells and the synaptic specializations of these hair cells are preserved after intratympanic gentamicin treatment in chinchillas using light and transmission electron microscopy. If such structural preservation is seen, it may provide a basis for the recovery of vestibular function noted in our human subjects. The second goal is to determine if central augmentation of gain occurs after intratympanic gentamicin treatment. This will be accomplished using direct galvanic stimulation of the VIIIth nerve after intratympanic gentamicin treatment. The nystagmus elicited by excitation of the nerve on the treated side should show an increased velocity compared to the control side if there is a central augmentation of gain. Understanding whether vestibular function partially recovers after intratympanic gentamicin treatment has important implications for the treatment of Meniere's disease, as preservation of function may become an important goal if vertigo remains controlled. Furthermore, the mechanisms of vestibular recovery may help us understand the potential for the inner ear to recover from a variety of injuries.