Effect of Noise Induced Hearing Loss on AVCN Principal Neurons

噪声性听力损失对 AVCN 主神经元的影响

• 批准号: 7486435
• 负责人: YONG WANG
• 金额: $ 5.4万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7486435
• 关键词: Ablation; Acoustic Nerve; Acoustics; Acute; Address; Affect; American; Animal Model; Anterior; Auditory; Auditory system; Brain Stem; Cell Nucleus; Cells; Chromosome Pairing; Chronic; Class; Cochlear nucleus; Code; Complement; Computer information processing; Condition; Control Animal; Cues; Data; Deterioration; Devices; Environment; Exhibits; Frequencies; Genetic Predisposition to Disease; Hand; Hearing; Hearing Impaired Persons; Hyperactive behavior; Immunohistochemistry; Inbred CBA Mice; Inbred DBA Mice; Individual; Intervention; Knowledge; Labyrinth; Learning; Life; Long-Term Effects; Mammals; Measures; Mouse Strains; Mus; Nerve Fibers; Neurons; Noise; Noise-Induced Hearing Loss; Outcome; Peripheral; Pharmaceutical Preparations; Physiological; Play; Potassium Channel; Preparation; Presbycusis; Process; Proteomics; Role; Slice; Sound Localization; Synapses; Synaptic Transmission; Synaptic Vesicles; Techniques; Testing; Tissues; Training; Week; Work; auditory pathway; auditory threshold shift; deafness; early onset; hazard; hearing impairment; postsynaptic; presynaptic; receptor function; research study; response; speech recognition; stem; transmission process; voltage

More than 10 million Americans suffer from noise induce hearing loss (NIHL). Short and long term noise exposure is a major hazard in certain "normal" working and living environments. Noise exposure, depending on intensity and duration, can result in temporary or permanent auditory threshold shift (TTS, PTS). Recent studies have shown that synaptic efficacy deteriorates at the endbulb synapse in the anterior ventral cochlear nucleus (AVCN) in a strain of mice with age related hearing loss. Furthermore, there is a functional reduction of entrainment to high frequency stimulation in postsynaptic bushy neurons. These changes are likely due to diminished activity in the afferent auditory nerve fibers. Noise insults, on the other hand, generate recurring short term hyperactivity in the auditory nerve. The excessive excitation could have detrimental effect on the endbulb synapse and its postsynaptic target. Because the AVCN provides vital cues to higher auditory centers for sound localization and speech recognition, it is essential to understand the functional consequences of noise induced hearing loss at this first relay synapse. Thus, we propose 2 specific aims. In the first aim, we will explicitly test the hypothesis that synaptic efficacy at the endbulb terminal is impaired immediately following noise exposure. However, the efficacy recovers with moderate insults resulting in only TTS, whereas the efficacy becomes permanently reduced in NIHL with PTS. We will take advantage of the low individual variability in noise exposure outcome in inbred CBA mice. Using a modified whole cochlear nucleus slice preparation, we will probe several aspects of synaptic transmission with electrophysiological recordings after noise overexposure. In the second aim, we will test the hypothesis that noise induced hearing loss affects the low threshold K+ conductance (lLr) in the postsynaptic bushy neurons; this effect in turn reduces the temporal coding capability in these neurons. We will characterize the rfrom bushy cells after inducing NIHL, and test the fine temporal coding of the bushy cell by activating the auditory nerve fiber with a realistic Poisson distributed spike train in the slice. Data from this project will complement and enhance the existing wealth of information regarding the peripheral effect of noise induced hearing loss. Ultimately we would like to address whether the integrity of the central auditory pathway can be preserved with drug or device intervention after NIHL, because CNS functional integrity is an essential component of successful post hearing loss intervention.

超过1000万美国人患有噪音引起的听力损失（NIHL）。短期和长期噪音