NEUROBIOLOGY OF THE VENTRAL COCHLEAR NUCLEUS IN DEAFNESS

耳聋腹侧耳蜗核的神经生物学

• 批准号: 6175680
• 负责人: Howard W Francis
• 金额: $ 11.72万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6175680
• 关键词: action potentials; brain stem; cerebellum; cochlea; deafness; electrical potential; electrophysiology; laboratory rat; neurobiology; neurons; voltage /patch clamp

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.

本文对耳聋患者耳蜗核的电生理进行了研究。 作为整体职业发展计划的一部分提出供资 获得临床科学家发展指导奖 候选 提出了教学学习和研究经验的结合， 听力科学中心和耳鼻喉科， 约翰霍普金斯大学，由Paul Manis博士赞助。的 候选人是一个神经耳科医生与疾病的特殊兴趣， 听觉系统 提出了一项研究， 中枢适应的功能后果和细胞机制 耳聋。 已经组织了一个职业计划， 完成他的研究所需的生物物理和数学技能 目标和长期目标，包括使用体外数据 表征和模拟耳聋的中枢听觉机制。 这 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。 双侧耳蜗消融术的电生理效应将是 在老鼠身上研究。 在第一个目标的实验中， 鉴定的VCN神经元将经历细胞内电流钳 脑干切片中的记录来测试耳蜗 烧蚀改变了电性能和放电特性 这些神经元。初步研究显示， 去传入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， 静息膜电位降低，电流-电压升高 II型（丛状）细胞中的整流。 第二个目标的实验 将评估改变的电特性如何区分 星状细胞和丛状细胞影响其编码特性，通过研究 它们对一连串短电流脉冲的反应， 听觉神经纤维对声音刺激的反应。 初步研究 建议声幅度调制的表示， 星状细胞和丛状细胞的相位锁定受损， 耳蜗消融术 第三个目标的实验将检验 假设在电和编码特性的变化， 去传入VCN神经元与钠的改变有关， 通过紧密密封全细胞电压钳测量的钾电导 在脑干切片和急性分离的细胞中进行记录 准备工作。