Behavioral Tests for Mouse Models of Autism: An Argument for the Inclusion of Cerebellum-Controlled Motor Behaviors

• Published in: Neuroscience 2021-05, Vol.462, p.303-319
• Main Authors: Simmons, Dana H., Titley, Heather K., Hansel, Christian, Mason, Peggy
• Format: Article
• Language: English
• Subjects: Animals; autism; Autism Spectrum Disorder; Autistic Disorder; Behavior Rating Scale; Cerebellum; delay eyeblink conditioning; Disease Models, Animal; Humans; Mice; motor learning; social behavior
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2020.05.010

•Mouse models constitute an essential experimental tool in the study of brain developmental disorders.•Here, we discuss behavioral tests that are used to phenotypically describe mouse models of autism spectrum disorder (ASD).•We critically evaluate these tests regarding behavioral relevance and knowledge about brain circuits involved.•We argue that motor behaviors complement test suites for social behaviors well as they often are evolutionary conserved. 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. 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.