New genetic technology has created a need for detecting changes in behavior caused by a wide variety of mutations. The goal of this project is to devise an optimal array of tests of two behavioral domains in mice, motor coordination/ataxia and learning/memory, and then demonstrate the value of these tests in a study of alcohol and fluoxetine effects on behavior tested simultaneously in two laboratories. To define the optimal array, a large number of tests will first be administered to a small number of standard mouse strains, none of which is markedly abnormal. The best of these tests will then be given simultaneously with identical apparatus and procedures in two laboratories to a large number of inbred strains, some of which have mild neurological abnormalities. This will allow us to eliminate any tests that are (a) highly correlated between strains and therefore redundant in the context of genetic screening research, (b) too sensitive or altogether insensitive to certain neurological abnormalities, or (c) too sensitive to minor environmental differences between laboratories. Finally, the refined and optimal array of behavioral tests will be used to assess effects of drugs in the two labs simultaneously. To achieve these ends, a video image analysis system will achieve high-throughput data collection and analysis by monitoring several kinds of apparatus asynchronously. The apparatus designs, testing protocols, and computer programs will be made available to other investigators, and the extensive data on inbred strains will be entered into a central database. A detailed training manual will be compiled, including norms for results when the tests are done properly with normal and abnormal mice. Designs, protocols, and data for the standardization sample will also be made available through a website. The tests will be especially useful to investigators interested in screening chemically-induced and transgenic mutations for multiple behavioral effects.
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