C57BL/6 mice consistently outperform DBA/2 mice in a range of hippocampal-dependent spatial learning behaviors. We recorded evoked responses from the dentate gyrus of awake, freely-moving mice and measured synaptic plasticity (LTP) and performance in a hippocampal-dependent task in individual animals from these two inbred strains. Spatial alternation tasks confirmed the behavioral divergence between the two strains, with C57BL/6 mice demonstrating more robust alternation than DBA/2 mice. Recording changes in field potentials in the dentate gyrus following three different high-frequency stimulation paradigms in the same groups of animals revealed differences in neural plasticity: both strains were able to support long-term potentiation (LTP) at perforant path synapses, but brief high-frequency stimulation induced larger and longer potentiation of the population spike in C57BL/6 than in DBA/2 mice. This greater propensity for population-spike potentiation in the strain that performed better in a hippocampal-dependent task is in accord with the different neurochemical profiles of C57BL/6 and DBA/2 mice.