Department of Neurobiology, University of Pittsburgh; Center for Neuroscience, University of Pittsburgh.
Department of Neurobiology, University of Pittsburgh; Center for Neuroscience, University of Pittsburgh; Center for Neural Basis of Cognition, University of Pittsburgh.
J Vis Exp. 2023 Jan 6(191). doi: 10.3791/64581.
Noise exposure is a leading cause of sensorineural hearing loss. Animal models of noise-induced hearing loss have generated mechanistic insight into the underlying anatomical and physiological pathologies of hearing loss. However, relating behavioral deficits observed in humans with hearing loss to behavioral deficits in animal models remains challenging. Here, pupillometry is proposed as a method that will enable the direct comparison of animal and human behavioral data. The method is based on a modified oddball paradigm - habituating the subject to the repeated presentation of a stimulus and intermittently presenting a deviant stimulus that varies in some parametric fashion from the repeated stimulus. The fundamental premise is that if the change between the repeated and deviant stimulus is detected by the subject, it will trigger a pupil dilation response that is larger than that elicited by the repeated stimulus. This approach is demonstrated using a vocalization categorization task in guinea pigs, an animal model widely used in auditory research, including in hearing loss studies. By presenting vocalizations from one vocalization category as standard stimuli and a second category as oddball stimuli embedded in noise at various signal-to-noise ratios, it is demonstrated that the magnitude of pupil dilation in response to the oddball category varies monotonically with the signal-to-noise ratio. Growth curve analyses can then be used to characterize the time course and statistical significance of these pupil dilation responses. In this protocol, detailed procedures for acclimating guinea pigs to the setup, conducting pupillometry, and evaluating/analyzing data are described. Although this technique is demonstrated in normal-hearing guinea pigs in this protocol, the method may be used to assess the sensory effects of various forms of hearing loss within each subject. These effects may then be correlated with concurrent electrophysiological measures and post-hoc anatomical observations.
噪声暴露是感音神经性听力损失的主要原因。噪声诱导听力损失的动物模型为听力损失的潜在解剖和生理病理学提供了机制上的见解。然而，将人类听力损失中观察到的行为缺陷与动物模型中的行为缺陷联系起来仍然具有挑战性。在这里，瞳孔测量法被提议作为一种能够使动物和人类行为数据直接比较的方法。该方法基于一种改良的Oddball 范式——使受试者习惯于重复呈现刺激，并间歇性地呈现在某些参数方面与重复刺激不同的偏差刺激。基本前提是，如果受试者检测到重复刺激和偏差刺激之间的变化，它将触发比重复刺激更大的瞳孔扩张反应。该方法使用豚鼠的发声分类任务进行了演示，豚鼠是听觉研究中广泛使用的动物模型，包括听力损失研究。通过将来自一个发声类别作为标准刺激的发声和另一个类别作为嵌入噪声中的异常刺激呈现，证明了对异常刺激类别的瞳孔扩张程度与信噪比单调变化。然后可以使用生长曲线分析来描述这些瞳孔扩张反应的时间过程和统计学意义。在本方案中，详细介绍了使豚鼠适应设置、进行瞳孔测量以及评估/分析数据的程序。虽然该技术在本方案中演示了正常听力的豚鼠，但该方法可用于评估每个受试者中各种形式的听力损失的感觉效果。然后可以将这些效果与并发的电生理测量和事后解剖学观察相关联。
