Controlled Enhancemnt of Long-Term Memory by Modulating Neuronal miRNA Function
Final rept. 1 Nov 2007-30 Apr 2009
SCIENCE APPLICATIONS INTERNATIONAL CORP SAN DIEGO CA
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The modulation of long-term memory formation in a mouse model has been evaluated following administration of antisense oligonucleotides targeting mRNA from Calcineurin, p250GAP, Armitage, Cbl-b, and CREB-BP in the brain. Alzet minipumps containing stable phosphorothioate antisense oligonucleotides for the 5 targets and a control oligonucleotide were implated in the brains of 51 C57B16 male mice. Following recovery, animals were trained for 3 days, and memory formation was assessed after 3 days, 3 weeks, and 7 weeks. Sustained knock-down of Cbl-b statistically enhanced 24 hr and 3 week memory, but produced histological changes in the brains of treated animals.