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Target: ADDL Synuclein? LTP or LTD ADDL reduce LTP Disease relevance Mouse models K-channels A-current Proteins Genes Gene expression patterns ModelDB BrainPharm GenSat AllenBrain PubMed How does ADDL impair synaptic plasticity? Does LTP occur in the right place? What is the mechanism? What cell types are affected? Right cell type? Go to slide 3 What genes and proteins are involved? Go to next slide Channel cell type Which genes are expressed in the relevant part of the brain? Synuclein reduces LTP? Dataset/ Source: SWAN Questions: What form of Abeta cause AD? Alzgene 2: driving question How does ADDL impair synaptic plasticity? What cell types are affected? Brings to mechanism question Brain Pharm ADCA1 NeuronDB CA1extracellular Abeta CA1has currentA-current A-currenthas channelK+ Missing datasets Currents that have K+ ions are conducting K+ channels? CA1LTP 3: mechanisms K-channels proteins K-channels genes CA1LTP LTPpapers MeSH “LTP” and “K-channel” colocalization network PubMed : Kv4.2 pmid: 17122039 PaperGene Orthomap AlzGene: Potassium channel gene HilleWashUch annel database EntrezgenePub Med GeneRIFSPubM ed Jax synaptic plasticity Jax hippocampal biology