Twin studies have shown a strong genetic basis for autism spectrum disorders (ASD). However, genetic analyses to determine specific genetic factors responsible for ASD have suggested that the majority of cases involve complex interactions between multiple genes and possible environmental factors.
ASD is diagnosed mainly on the basis of abnormal behaviors including impaired social interaction and communication, and by restricted and repetitive behavior.
Mouse models of psychiatric diseases, such as ASD, are useful tools for investigating the mechanisms of the human disorders and for screening of therapeutic approaches to those disorders. Different mouse lines bearing mutations in genes linked to ASD have recently been generated aiming to allow better understanding the relationship between ASD behavioral symptoms to the genotype (genetic background). This is largely done by assaying these mutant mouse models in different behavioral assays and searching for behavioral abnormal that resemble some of the core symptoms of ASD.
Surprisingly, despite the clear deficiencies in social interactions exhibited by ASD patients, social behaviors have been tested to only a limited extent in most of the mutant mouse models utilized in studies of ASD. One of the major obstacles in this field is that the set of mouse behavioral tasks defined as being relevant to the symptoms of autism and suitable for application across mouse models is very limited, particularly with respect to social interactions. Furthermore, social behavior by mice generally needs to be manually evaluated, which is laborious and requires a high level of training and resources. Thus, there is a growing scientific consensus that, to obtain a deep understanding of social behavior in normal and mutant mouse models used in ASD research, it is vital to develop standardized tools to allow quantify a multitude of complex mouse behaviors. Specifically, there is a great need for a system suitable for large-scale behavioral screening that is easy and reliably to use across different mouse strains, research groups, and experimental assays.
In this project, we propose to develop a research tool that combine surveillance video system with radiotelemetry tracking system that will allow to automatically identify and quantify a wide range of mouse behaviors, including social behaviors, in freely interacting mouse populations, while providing the animals with a rich social and sensory environment resembling that which exists in natural habitat. Furthermore, we will design a simple behavioral procedure to be used with the automated behavioral phenotyping system that can be uniformly applied across mouse models and research teams. Thus, it will provide researchers in different groups around the world that study ASD with a much needed "common language" to use when comparing the results of their research.
Such behavioral paradigm can be used to, first, characterize large battery of abnormal behavioral function that are relevant to behavioral symptoms of ASD including low level of exploration behavior, high social avoidance, elevated stereotypic behavior, and increased anxiety-like behavior. Second, it will allow increasing the knowledge of the interaction between genes and environmental factors underlying susceptibility for autism.
In the long term, the experimental system to be developed in this project may pave the way to identify additional genetic factors linked to ASD as well as serving as a preclinical tool to evaluate drug treatments and behavioral treatments for ASD.