The activities of this Core will provide services to all projects in the characterization of behavioral phenotypes/endophenotypes of mice under study as models for the molecular genetics of schizophrenia. This core will utilize the Neurogenetics and Behavior Center (NBC), a unique resource contributing to NIH supported research programs using mouse models and gene targeting technology to study basic functions of the brain and disorders relevant to psychiatric and neurological disease. As such, the behavioral studies in the facility are integral to bridging from genomic/molecular/cellular levels of analysis to the study of behavioral systems and functional disorders. In its past 4 years of operation, NBC has established and optimized over 80 protocols for behavioral assessments in 3 primary domains: cognitive functions, affective motivational processes, and sensorimotor integration. We draw on this repertoire of behavioral technology in the Core plan. Initial screening of mice in the research program overall will be conducted within the phenotyping facilities at the Broadway Research Building (BRB) where the mice will be generated and housed for use in Projects 1-3. These protocols will include 1) a basic battery for neurological assessment, 2) activity assessments including tests in environments that yield generalized affective measures (e.g. plus maze), 3) a well-characterized assessment for sensorimotor gating (pre-pulse inhibition). Additional test mice will be generated within the BRB facilities for extensive behavioral analysis in the NBC facilities;these test subjects will be transferred at appropriate ages in numbers required for the experimental design of studies described herein. The proposed behavioral assessments at NBC are chosen to target the neurodevelopmental trajectory of disease and directed to key neural circuitry that appears most affected in this disorder. Thus we focus on specific behavioral protocols to assess limbic and cortical (particularly prefrontal) circuits. A cross-cutting behavioral platform to identify endophenotypes in these mouse models will include context and trace conditioning (hippocampal system), latent inhibition (hippocampal and forebrain dopamine systems), reversal learning and reinforcer devaluation (prefrontal function) and working memory/recognition memory assessments (temporal lobe and prefrontal circuits). A particular advantage of testing in the Core resource is not only to serve the specific objectives of the individual projects within this research program but to acquire datasets using common behavioral protocols across models of neuropsychiatric disease. Through the datasharing provisions of the NBC, once published, the results of this research will be accessible to the broad scientific community.
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