NEUROBIOLOGY OF THE VENTRAL COCHLEAR NUCLEUS IN DEAFNESS

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A study of the electrophysiology of the cochlear nucleus in deafness is being proposed as part of an overall career development plan for funding by a Mentored Clinical Scientist Development Award. The candidate proposes a combination of didactic learning and research experience in the Center for Hearing Science and the department of Otolaryngology at Johns Hopkins University under the sponsorship of Paul Manis, Ph.D. The candidate is a neurotologist with a special interest in disorders of the auditory system. A research study is proposed to characterize the functional consequences and cellular mechanisms of central adaptation to deafness. A career plan has been organized to provide the biophysical and mathematical skills needed to fulfill his research objectives and long-term goals, which include the use of in vitro data to characterize and model central auditory mechanisms in deafness. This research effort may provide insights with clinical implications in the rehabilitation of hearing loss. The electrophysiological effects of bilateral cochlear ablation will be studied in rat. In experiments of the first aim morphologically identified VCN neurons will undergo intracellular current-clamp recordings in brainstem slices to test the hypothesis that cochlear ablation alters the electrical properties and discharge characteristics of these neurons. Preliminary studies show significant changes in the electrical properties of deafferented VCN neurons including the slowing of action potential repolarization in type 1 (stellate) cells, and a decrease in resting membrane potential and increase in current-voltage rectification in type II (bushy) cells. Experiments of the second aim will evaluate how the altered electrical properties of differentiate stellate and bushy cells affect their encoding properties, by studying their response to trains of brief current pulses that mimic the response of auditory nerve fibers to acoustic stimuli. Preliminary studies suggest that the representation of acoustic amplitude modulation by stellate cells, and phase locking by bushy cells are impaired following cochlear ablation. Experiments of the third aim will test the hypothesis that changes in the electrical and encoding properties of deafferented VCN neurons are associated with alterations in sodium and potassium conductance as measured by tight-seal whole-cell voltage-clamp recordings performed in both brainstem slice and acutely isolated cell preparations.