The long term goal of this proposal is to develop human models of deafferentation by studying the morphological and neurochemical changes secondary to specific lesions within the vestibular periphery. Two models are used in this study I: A lesion of Scarpa~s Ganglion and II: A lesion Affecting the Endorgans. A combination of classical histological techniques, immunohistochemistry, electron microscopy, molecular biologic techniques, and computer based quantitative analyses will be used to document the changes. One unique aspect of the present proposal is that a wide variety of human temporal bone and brain stem specimens are available for this study, including autopsy, archival and surgical specimens. This study will focus on specimens from patients in a chronic compensated state following a lesion of the vestibular periphery. Critical information regarding the following phenomenon in human vestibular periphery will be obtained: 1) Is there a dependency of the vestibular neuroepithelium on the vestibular nerve for survival? 2) Reciprocally, is the vestibular nerve dependent on the vestibular hair cells for survival? 3) Does retrograde degeneration occur in the presence of intact afferent dendrites? 4) Is there a subtype of calretinin immunoreactive Scarpa~s ganglion neuron which is resistant to retrograde degeneration? 5) Is there a qualitative correlation between the amount of degeneration in the endorgans and in Scarpa's ganglion? Within the vestibular nuclear complex (VNC), important data will be gathered on : 1) Does retrograde degeneration affect the central processes of the vestibular nerve after a lesion of the vestibular periphery? 2) Is there a permanent loss of synaptic density in the ipsilateral VNC after a lesion of Scarpa's ganglion and/or the endorgans? 3) is there an altered expression of glutamic acid decarboxylase (GAD), N-methyl-D-aspartate (NMDA) receptor, or calretinin in the VNC in Chronic deafferented states? The MCSDA grant will allow me to develop proficiency at using molecular biologic techniques and quantitative morphologic studies to human tissue specimens which is needed to establish myself as an academic neurotologist, specifically within the field of human temporal bone and brain stem pathology and neurochemistry
