NEUROBIOLOGY OF THE VENTRAL COCHLEAR NUCLEUS IN DEAFNESS

耳聋耳蜗核电生理学的研究 被提议作为资助的总体职业发展计划的一部分 荣获指导临床科学家发展奖。 候选人 提出将教学学习和研究经验相结合 听力科学中心和耳鼻喉科 约翰霍普金斯大学在 Paul Manis 博士的赞助下的 候选人是一位神经病学家，对神经疾病特别感兴趣 听觉系统。 提出一项研究来描述 中枢适应的功能后果和细胞机制 至耳聋。 已制定职业计划，以提供 完成他的研究所需的生物物理和数学技能 目的和长期目标，包括体外数据的使用 表征和模拟耳聋的中枢听觉机制。 这个 研究工作可能会提供具有临床意义的见解 听力损失的康复。 双侧耳蜗消融的电生理效应将是 在大鼠身上进行了研究。 在第一个目标形态学的实验中 确定的 VCN 神经元将经历细胞内电流钳 脑干切片中的录音以检验耳蜗的假设 烧蚀改变了电特性和放电特性 这些神经元。初步研究显示显着变化 失传入神经元 VCN 神经元的电特性，包括减慢 1 型（星状）细胞的动作电位复极化，以及 静息膜电位降低和电流电压增加 II 型（浓密）细胞的校正。 第二个目标的实验 将评估改变后的电特性如何区分 通过研究星状细胞和丛状细胞影响它们的编码特性 他们对模拟响应的短暂电流脉冲序列的响应 听觉神经纤维对声刺激的影响。 初步研究 建议声幅度调制的表示为 星状细胞和丛状细胞的锁相在以下情况下受损 耳蜗消融术。 第三个目标的实验将测试 假设电气和编码特性发生变化 传入神经阻滞的 VCN 神经元与钠和 通过密封全细胞电压钳测量钾电导 在脑干切片和急性分离的细胞中进行记录 准备工作。

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.