Simmons Dana H, Titley Heather K, Hansel Christian, Mason Peggy
Department of Neurobiology, The University of Chicago, Chicago, IL, USA.
Department of Neurobiology, The University of Chicago, Chicago, IL, USA.
Neuroscience. 2021 May 10;462:303-319. doi: 10.1016/j.neuroscience.2020.05.010. Epub 2020 May 15.
Mouse models of Autism Spectrum Disorder (ASD) have been interrogated using a variety of behavioral tests in order to understand the symptoms of ASD. However, the hallmark behaviors that are classically affected in ASD - deficits in social interaction and communication as well as the occurrence of repetitive behaviors - do not have direct murine equivalents. Thus, it is critical to identify the caveats that come with modeling a human disorder in mice. The most commonly used behavioral tests represent complex cognitive processes based on largely unknown brain circuitry. Motor impairments provide an alternative, scientifically rigorous approach to understanding ASD symptoms. Difficulties with motor coordination and learning - seen in both patients and mice - point to an involvement of the cerebellum in ASD pathology. This brain area supports types of motor learning that are conserved throughout vertebrate evolution, allowing for direct comparisons of functional abnormalities between humans with autism and ASD mouse models. Studying simple motor behaviors provides researchers with clearly interpretable results. We describe and evaluate methods used on mouse behavioral assays designed to test for social, communicative, perseverative, anxious, nociceptive, and motor learning abnormalities. We comment on the effectiveness and validity of each test based on how much information its results give, as well as its relevance to ASD, and will argue for an inclusion of cerebellum-supported motor behaviors in the phenotypic description of ASD mouse models. LAY SUMMARY: Mouse models of Autism Spectrum Disorder help us gain insight about ASD symptoms in human patients. However, there are many differences between mice and humans, which makes interpreting behaviors challenging. Here, we discuss a battery of behavioral tests for specific mouse behaviors to explore whether each test does indeed evaluate the intended measure, and whether these tests are useful in learning about ASD.
为了了解自闭症谱系障碍（ASD）的症状，人们使用了各种行为测试对ASD小鼠模型进行研究。然而，ASD中典型受影响的标志性行为——社交互动和沟通缺陷以及重复行为的出现——在小鼠中并没有直接对应的行为。因此，识别在小鼠中模拟人类疾病所带来的注意事项至关重要。最常用的行为测试代表了基于 largely未知脑回路的复杂认知过程。运动障碍为理解ASD症状提供了一种替代的、科学严谨的方法。在患者和小鼠中都观察到的运动协调和学习困难表明小脑参与了ASD病理过程。这个脑区支持在整个脊椎动物进化过程中保守的运动学习类型，从而能够直接比较自闭症患者和ASD小鼠模型之间的功能异常。研究简单的运动行为为研究人员提供了清晰可解释的结果。我们描述并评估了用于小鼠行为测定的方法，这些测定旨在测试社交、沟通、固执、焦虑、伤害感受和运动学习异常。我们根据每个测试结果所提供的信息量以及其与ASD的相关性来评论每个测试的有效性和效度，并主张将小脑支持的运动行为纳入ASD小鼠模型的表型描述中。
自闭症谱系障碍小鼠模型帮助我们深入了解人类患者的ASD症状。然而，小鼠和人类之间存在许多差异，这使得行为解释具有挑战性。在这里，我们讨论了一系列针对特定小鼠行为的行为测试，以探讨每个测试是否确实评估了预期的指标，以及这些测试在了解ASD方面是否有用。
