Behavioral and physiological measurements of hearing in mouse models of Alzheimer's Disease

项目摘要 虽然阿尔茨海默氏病和相关痴呆症（ADRD）和听力损失通常同时发生，但其性质 这种关系在很大程度上仍然是未知的。已经开发了许多小鼠模型以更好地理解 生理和行为的影响，具体的ADRD相关的大脑病理，但研究听力 在这些小鼠中的研究滞后于人类研究，并且没有产生明确的结果， laboratories.一项研究表明，暴露于有害的噪音可能会加剧ADRD病理 在一个ADRD模型小鼠品系中，但其他实验室在其他小鼠品系中没有发现类似的效果。 此外，大多数研究人员在小鼠模型中寻找关于听力，听力损失和衰老的信息， ADRD利用麻醉小鼠的生理学方法或反射方法来评估听力状态。 虽然这些技术是信息，没有一种方法准确地描绘了如何清醒，行为 有机体感知周围的世界。这一点至关重要，因为流行病学和听力学研究 患有ADRD的人以及健康老龄化的人主要依赖听力的行为测量 功能障碍因此，在小鼠寿命的几个时间点， 使用行为心理声学评估和生理诱发的三种ADRD小鼠模型 潜在的技术将被使用。比较用以下方法训练的雄性和雌性小鼠的结果： 操作性条件反射和正强化的麻醉和未麻醉小鼠使用 将进行听觉脑干反应和中潜伏期反应记录。比较 生理测量的行为结果将提供关于行为是否 性能反映了中央补偿过程，生理测试条件对应于 行为缺陷这些实验将有助于更好地了解年龄，性别和噪音如何影响 小鼠的沟通，可能导致人类沟通问题的理解进展 患有ADRD的患者。

Project Summary Although Alzheimer’s disease and related dementias (ADRD) and hearing loss often co-occur, the nature of this relationship is still largely unknown. Many mouse models have been developed to better understand the physiological and behavioral effects of specific ADRD-related brain pathologies, but the research on hearing in these mice lags human studies and has not produced definitive results, with huge variability across laboratories. One study suggested that exposure to damaging noise may exacerbate the ADRD pathology in one ADRD model mouse strain, but other labs have not found similar effects in other mouse strains. Further, most researchers pursuing information about hearing, hearing loss, and aging in mouse models of ADRD utilize physiological methods in anesthetized mice or reflexive methods to assess hearing status. While these techniques are informative, neither method accurately portrays how an awake, behaving organism perceives the world around them. This is critical because epidemiological and audiological studies of humans with ADRD, as well as healthy-aging humans, rely primarily on behavioral measures of hearing dysfunction. For this reason, hearing in quiet and in noise at several time points in the mouse lifespan in three mouse models of ADRD using behavioral psychoacoustic assessments and physiological evoked potential techniques will be conducted. Comparisons of results from male and female mice trained with operant conditioning and positive reinforcement to those from anesthetized and unanesthetized mice using auditory brainstem response and middle latency response recordings will be made. Comparisons of behavioral results to physiological measurements will provide information about whether behavioral performance reflects central compensation processes and which physiological test conditions correspond to behavioral deficits. These experiments will help to better appreciate how aging, sex, and noise affect communication in mice, possibly leading to advances in understanding communication issues in human patients suffering from ADRD.