Late-LTP but not early-LTP activates hippocampal precursors in vitro. To narrow down the mechanisms of LTP that underlie the activation of precursors, we investigated the ability of early-LTP (n=3) and late-LTP (n=3) to activate precursors using the neurosphere assay, 2 days after stimulation. (a) Data showing the mean fEPSP slope (±s.e.m.) as a percentage of baseline. Mice assigned to early-LTP group showed a 139.0±5.8% increase in the fEPSP response 10 min after HFS. However, this potentiation did not persist, and decayed to baseline within 60 min (104.0±3.7% at 60 min after HFS, and 101.4±10.4% at 160 min after HFS). The late-LTP group showed robust LTP at all time points analyzed (171.3±6.4%, 153.4±16.9% and 163.1±17.4%, respectively). At the end of recording, the magnitude of potentiation in the late-LTP group was significantly greater than the early-LTP group (P<0.0001, Student's t-test). (b) Following the induction of late-LTP, a significant increase in the number of neurospheres was observed in the low K+ condition, compared with the early-LTP group (P=0.0051, Student's t-test with Welch's correction). (c) The magnitude of LTP, calculated 60 min after HFS, showed a significant positive correlation (r=0.879, n=15, P<0.0001, Pearson's correlation) with the number of neurospheres grown in vitro, after hippocampi were dissected 2 days after HFS. Arrow indicates HFS, error bars indicate s.e.m., low: low K+, high: high K+. **P<0.01, ***P<0.001. Abbreviations: fEPSP, field extracellular postsynaptic potential; HFS, high-frequency stimulation; LTP, long-term potentiation.