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更新豚鼠动物模型,用于低频听力范围内的体内听觉神经科学研究。

Updates to the guinea pig animal model for in-vivo auditory neuroscience in the low-frequency hearing range.

机构信息

Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA; Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.

Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA; Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA; Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA.

出版信息

Hear Res. 2022 Oct;424:108603. doi: 10.1016/j.heares.2022.108603. Epub 2022 Sep 5.

Abstract

For gaining insight into general principles of auditory processing, it is critical to choose model organisms whose set of natural behaviors encompasses the processes being investigated. This reasoning has led to the development of a variety of animal models for auditory neuroscience research, such as guinea pigs, gerbils, chinchillas, rabbits, and ferrets; but in recent years, the availability of cutting-edge molecular tools and other methodologies in the mouse model have led to waning interest in these unique model species. As laboratories increasingly look to include in-vivo components in their research programs, a comprehensive description of procedures and techniques for applying some of these modern neuroscience tools to a non-mouse small animal model would enable researchers to leverage unique model species that may be best suited for testing their specific hypotheses. In this manuscript, we describe in detail the methods we have developed to apply these tools to the guinea pig animal model to answer questions regarding the neural processing of complex sounds, such as vocalizations. We describe techniques for vocalization acquisition, behavioral testing, recording of auditory brainstem responses and frequency-following responses, intracranial neural signals including local field potential and single unit activity, and the expression of transgenes allowing for optogenetic manipulation of neural activity, all in awake and head-fixed guinea pigs. We demonstrate the rich datasets at the behavioral and electrophysiological levels that can be obtained using these techniques, underscoring the guinea pig as a versatile animal model for studying complex auditory processing. More generally, the methods described here are applicable to a broad range of small mammals, enabling investigators to address specific auditory processing questions in model organisms that are best suited for answering them.

摘要

为了深入了解听觉处理的一般原理,选择其自然行为涵盖正在研究过程的模式生物至关重要。这种推理导致了各种听觉神经科学研究的动物模型的发展,如豚鼠、沙鼠、龙猫、兔子和雪貂;但近年来,在小鼠模型中出现了先进的分子工具和其他方法,导致对这些独特的模型物种的兴趣减弱。随着实验室越来越多地将体内成分纳入其研究计划,全面描述将这些现代神经科学工具应用于非小鼠小型动物模型的程序和技术,将使研究人员能够利用可能最适合测试其特定假设的独特模型物种。在本文中,我们详细描述了我们为将这些工具应用于豚鼠动物模型以回答有关复杂声音(如发声)的神经处理问题而开发的方法。我们描述了发声获取、行为测试、听觉脑干反应和频率跟随反应记录、包括局部场电位和单个单元活动的颅内神经信号以及允许光遗传操纵神经活动的转基因的表达的技术,所有这些都在清醒和头部固定的豚鼠中进行。我们展示了可以使用这些技术在行为和电生理水平上获得的丰富数据集,强调了豚鼠作为研究复杂听觉处理的多功能动物模型。更一般地说,这里描述的方法适用于广泛的小型哺乳动物,使研究人员能够在最适合回答问题的模型生物中解决特定的听觉处理问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da85/9922531/025f5f269145/nihms-1866921-f0001.jpg

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