Most popular Overexpression of SIRT1 in hippocampus does not alter LTP or associative memory. A , Western blot shows ∼16-fold SIRT1 protein increase in hippocampus of NeSTO mice compared with control Nestin–Cre animals. The numbers below show SIRT1 levels relative to actin. B , I/O curve of field EPSP slope versus current input (microamperes) is shifted to the left in NeSTO mice (n = 14; gray circles) compared with Nestin–Cre (n = 10; black circles; p < 0.0001, two-way ANOVA), suggesting increased basal synaptic excitability. C , Paired-pulse facilitation reveals normal presynaptic events in NeSTO mice (n = 5 each genotype). D , Similar LTP was elicited by 5 × 3 and 10 × 10 TBS (EPSP slopes; n = 7 each genotype) in mice overexpressing wild-type or increased levels of SIRT1. E, F , Fear conditioning to context ( E ) or tone ( F ) in Nestin–Cre (n = 14) and NeSTO animals (n = 18) show similar associative learning capacities in both strains. Data represent means ± SEM. 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