Mouse Model Of Autistic Repetitive Behavior

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DESCRIPTION (provided by applicant): The presence of abnormal repetitive behaviors is necessary for a diagnosis of autism. These behaviors can be distressing, self-injurious, and difficult to treat. Despite their importance however, abnormal repetitive behaviors have received far less attention from researchers than other symptoms of autism. The specific goal of this project is therefore to develop an animal model of abnormal repetitive symptoms in autism. Abnormal repetitive behaviors in autistic patients are associated with disruption of 'executive' systems which are responsible for selecting and sequencing behavior. The performance of different executive systems can be measured using distinct neuropsychological tasks. Abnormal repetitive behavior in autism can be divided into 'high-level' behaviors which correlate with impairments in 'high-level' executive systems, measured using the IDED task; and 'low-level' behaviors which correlate with impairments in 'low-level' executive systems, measured using the gambling task. Abnormal repetitive behaviors commonly develop in captive animals. C57BL6/J laboratory mice perform two kinds - barbering (hair-pulling), and stereotypy - that closely resemble 'high-level' and 'low-level' behaviors respectively in autistic patients. If these behaviors are indeed equivalent to autistic symptoms they should correlate with the same measures of executive dysfunction. We will use a number of cognitive tasks, including the IDED and gambling tasks, to measure executive dysfunction in the mice. Our specific aims are therefore to: 1) develop standardized methods for recording these behaviors and performing these tasks in mice; 2) test the prediction that barbering will correlate with impairments on the IDED tasks; and 3) test the prediction that stereotypy will correlate with impairment on the gambling task. Developing a model of these symptoms in mice opens up several exciting new avenues for future research into environmental factors, genetic factors, and possible therapies.