CORE 1: Genetically Engineered Mice for Collaborations

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Many Individual Projects of the proposed Silvio O. Conte Center for Neuroscience Research (CCNR) at MIT utilize genetically engineered mice as key experimental tools. Most of these mouse strains are conditionally engineered (i.e., spatially and/or temporally restricted) and, hence, require state-of-the-art technology. The role of Core #1 is twofold: to provide the technical knowhow regarding the transgenics and knockout mice to the Center's individual laboratories and to generate some of the strains that are proposed to be used by the Center's multiple laboratories as multidisciplinary collaborations. In Specific Aims #1 to #3, the Cre-loxP recombination system will be combined with the tetracycline-transactivator (tTA) system to accomplish cell type-restricted, reversibly regulatable expression of a gene. Specific Aim #1 will attempt to regulate the NMDA receptor (NR)-1 gene in the dentate gyrus (DG) granule cells, while Specific Aim #2 will seek to regulate the GluR6 (G6) gene in the DG granule cells or CA3 pyramidal cells. These mutant mice provide invaluable tools in the Center's collaborative attempt (Individual Project #2) to understand the roles of synaptic plasticity in distinct hippocampal excitatory synapses in specific aspects of learning and memory. Specific Aim #3 will attempt to regulate the NR1 gene in the superficial layers of the entorhinal cortex and will serve the Center's collaborative effort (Individual Project #1) to understand the role of these receptors in place field formation. The objective of Specific Aim #4 is to produce a dorsal forebrain-restricted tTA mouse which is an important component mouse for the generation of multiple transgenic strains needed in the Center's collaborative attempt to understand how synaptic plasticity in the visual cortex subserves the receptive field plasticity (Individual Project #6). Core #1 will also provide training and the facility to Individual Project #7 which proposes to generate transgenic lines of PSD-GFP fusion proteins to study the morphological changes accompanying synaptic plasticity (Individual Project #7). Finally, Core #1 will provide advice and instructions to the attempt to genetically manipulate cortical function of monkeys (Individual Project #3).