The present proposal addresses two questions; 1) What are the cellular mechanisms determining the discharge properties of vestibular-nerve afferents? and 2) What are the distinctive contributions of the various kinds of afferents to the central processing of vestibular information? The two questions provide complementary perspectives on the vestibular nerve, since to understand a particular class of afferents requires knowledge of both the cellular mechanisms responsible for its discharge patterns and the use made of these patterns by the brain. The present proposal consists of four interrelated projects. Project 1 uses light- and electron-microscopy to investigate the regional organization of the vestibular organs in the chinchilla and the squirrel monkey. The goal is to relate the physiology of afferents with their afferent and efferent synaptic inputs. This is accomplished, in part, by ultrastructural reconstruction of labeled afferents, including some that have been physiologically characterized. Project 2 is a biophysical analysis of transduction mechanisms in the posterior crista of the turtle. This animal was chosen because we have had success in developing the required in vitro preparations. Also, the structural organization of the end organs suggests that the distinctive role of type I hair cells may be easier to discern in turtles than in mammals. The choice requires that we do morphological and physiological studies that parallel those already done in mammals. The biophysical studies will be done in an isolated epithelium, where normal anatomical relations can be maintained, and in solitary hair cells, where precise control of the extracellular and intracellular conditions can be maintained. In project 3, advantage is taken of recent advances in intracellular labeling technology to trace the central trajectories of individual, physiologically identified vestibular-nerve fibers from their origin in each of the five and organs in the chinchilla to their terminations in the vestibular nuclei, other brain-stem sites, and the cerebellum. In this way, we can ascertain if the various afferent classes differ in the spatial distribution of their endings or in the morphology of their axonal branches and terminals. The results should provide the anatomical basis for the segregation and convergence of different classes of afferent inputs in central pathways. Project 4 makes use of a recently devised method for rapidly and reversibly eliminating the discharge of irregularly discharging afferents in the alert squirrel monkey. The resulting functional ablation will be used to assess the contributions of these afferents to the overall operation of the angular and linear vestibulo-ocular reflexes, as well as to the discharge properties of secondary neurons, including those that are likely to contribute to the reflexes. The research program may provide insights into the etiology of vestibular disorders.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Hearing Research Study Section (HAR)
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University of Chicago
Schools of Medicine
United States
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