Core B: Animal Core Genetically modified mice offer many advantages for the multidisciplinary analysis of the mechanisms and functions of synaptic plasticity. They provide a renewable, reproducible and reliable resource that can be analyzed at multiple levels by multiple investigators with complementary expertise. Thus, a critical component of this program project is the use of the same lines of RIM mutant mice by all investigators. This will allow exploration of RIM function at multiple levels simultaneously, an approachwhich should synergistically lead to a more sophisticated understanding of the role of RIM proteins in active zone function and various forms of presynaptic plasticity. Importantly, by examining these mice behaviorally in well- defined assays of experience-dependent plasticity, we will also be able to probe the specific functional role of presynaptic LTP and the other forms of synaptic plasticity in which RIMs are involved. To accomplish this ambitious multidisciplinary approach will require a stable supply of correctly genotyped RIM mutant mice that can be used simulaneously by all members of the program project. The critical purpose of this animal core is to provide such animals. This Core will have two components, one at the Sudhof laboratory at UT Southwestern and one at Stanford. The UT Southwestern core will be responsible for the generation and initial characterization of the various mutant mice at the anatomical and biochemical levels. Mice will then be shipped to the Stanford Mouse Core B in which colonies will be established so that they can be examined in the cell biological, electrophysiological and behavioral assays described in Projects 2-4. Centralizing this function will achieve maximal efficiency both in terms of costs and labor and thus will greatly facilitate the overall progress of this program project.
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