Behavioral Assessment of Olivocochlear Activity in Mice

小鼠橄榄耳蜗活动的行为评估

• 批准号: 6803649
• 负责人: Cynthia A. Prosen
• 金额: $ 13.14万
• 依托单位: NORTHERN MICHIGAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6803649
• 关键词: acetylcholine; acoustic nerve; afferent nerve; auditory discrimination; auditory feedback; auditory nuclei; auditory stimulus; auditory threshold; behavior test; behavioral /social science research tag; biological models; cochlea; ear hair cell; efferent nerve; electrophysiology; genetically modified animals; histology; laboratory mouse; nicotinic receptors; noise; olivary body; olivocochlear bundle; psychophysics; psychophysiology; receptor expression; sound frequency

DESCRIPTION (provided by applicant): The long-term objective of this research project is to investigate the functional role of olivocochlear (OC) efferent feedback. The OC system originates in the superior olivary complex and projects both to the cochlea and the cochlear nucleus. The first specific aim will examine if efferent activity is instrumental in maintaining auditory attention. Experiments will be conducted with control and transgenic mice in which the gene encoding for the cochlear alpha9 nicotinic acetylcholine receptor (nAChR) subunits have been knocked out. Physiological studies have shown that these mutant mice exhibit normal afferent responses but show no obvious cochlear efferent activity because cholinergic OC projections cannot function in the absence of (9 receptor subunits. Subjects will perform a demanding listening task in which their auditory attention will be directed by a band-limited masker to a variable portion of the frequency spectrum. It is hypothesized that control mice will have better detection and discrimination rates for stimuli presented within the frequency region of the noise band masker compared to those presented outside of the band, while knock-out mice should have similar thresholds regardless of the center frequency of the noise band, since the latter mice should not be able to focus auditory attention. The second specific aim will differentiate contributions of central and peripheral efferent fibers to signal processing in noise, by comparing the hearing thresholds of (9 nAChR subunit normal knock-out mice with those of knock-outs whose OC projections to the cochlear nucleus have been surgical severed, in the same listening task described for Specific Aim 1. It is hypothesized that knockout subjects that lack only peripheral efferent innervations will hear better in this noisy, unpredictable environment compared to their cohorts that have central OC lesions in addition to peripheral de-efferentation. The final specific aim will evaluate the hypothesis that the OC efferent system protects the ear from acoustic over stimulation. Subjects used in these experiments will include control and transgenic mice that have an over expression of the cochlear alpha9 nAChR subunits. This novel transgenic preparation, in combination with planned electrophysiological and behavioral experimental methodologies, represents a unique opportunity to characterize the extent of the protection afforded by the OC system. A better understanding of the brain's acoustic feedback system will aid in the design of assertive devices for human listeners whose efferent function has been compromised.

描述（由申请人提供）：该研究项目的长期目标是研究橄榄石（OC）传出反馈的功能作用。 OC系统起源于上橄榄络合物，并投射到耳蜗和耳蜗核。第一个具体目的将检查传出活动是否有助于维持听觉的关注。实验将用对照和转基因小鼠进行，其中编码人工耳蜗α9烟碱乙酰胆碱受体（NACHR）亚基的基因被淘汰。生理研究表明，这些突变小鼠表现出正常的传入反应，但没有表现出明显的人工耳蜗传播活动，因为胆碱能的OC投影无法在没有（9个受体亚基。受体。受试者执行苛刻的听力任务，在这种情况下，他们的听觉注意力将被频繁的频率和频率的频率延伸到频率上。该频率越来越多。与在频带外呈现的频率区域相比，在噪声带掩蔽器的频率区域内呈现的刺激，而敲除鼠的阈值应与噪声频带的中心频率相似，因为后者小鼠应无法在中央和外围效果纤维中划分噪声的贡献，将其引起听觉的贡献。那些在针对特定目标1所描述的相同的聆听任务中，其OC对耳蜗核的预测已被切断的淘汰赛。据推测，与在这种嘈杂，不可预测的环境中相比，与具有外围性的环境相比，与具有外围性的环境相比，在外围噪声中，敲除受试者会听到更好的声音。最终的特定目的将评估OC源系统可保护耳朵免受声学过度刺激的假设。这些实验中使用的受试者将包括对照和转基因小鼠，这些小鼠对耳蜗α9NACHR亚基的过度表达。这种新型的转基因制剂结合了计划的电生理和行为实验方法，代表了一个独特的机会来表征OC系统提供的保护程度。对大脑的声学反馈系统的更好理解将有助于为人类听众的自信设备设计，他们的传出功能已受到损害。