Fig. 1

Hippocampal depotentiation in adult wild-type mice induced by theta-patterned stimuli. (a) After application of a single theta-burst-stimulation (TBS; indicated by arrow) to induce long-term-potentiation (LTP) in CA1 of 2–3 month-old C57Bl/6 J mice, the induction of depotentiation (DP) was attempted by delivery of theta-pulse-stimulation episodes (TPS; indicated by an open square) of either 2 min (DP 2; n = 9), 3 min (DP 3; n = 9), 5 min (DP 5; n = 7) or 8 min (DP 8; n = 7). While a ‘dose-response’ relationship could be observed, wherein longer TPS trains evoked increasingly stronger reversal of LTP, only DP 8 induced robust DP when compared to LTP controls (n = 10) (F _{(1, 15)} = 15.14, **p = 0.001). Error bars represent SEM. Traces show representative examples of field excitatory postsynaptic potentials (fEPSP) recorded during baseline, 1 min post-TBS delivery (IP 1 min), 1 min post-TPS delivery (DP 1 min), and 120 min post-TPS delivery (DP 120 min). Calibration bars: 0.5 mV and 5 ms. (b) Replicating same experiments with 6–9 month-old C57Bl/6 J mice revealed a susceptibility of DP to ageing. DP was not dependent on duration of TPS, since both DP 2 (n = 6) and DP 8 (n = 6) significantly reversed LTP (DP 2: F _{(1, 12)} = 4.867, *p = 0.047; DP 8: F _{(1, 12)} = 7.037, *p = 0.021), while DP 3 (n = 6) and DP 5 (n = 6) also showed a trend to significant DP when compared to LTP controls (n = 8) (DP 3: p = 0.073; DP 5: p = 0.074). Error bars represent SEM. Traces show representative examples of field excitatory postsynaptic potentials (fEPSP) recorded during baseline, 1 min post-TBS delivery (IP 1 min), 1 min post-TPS delivery (DP 1 min), and 120 min post-TPS delivery (DP 120 min). Calibration bars: 0.5 mV and 5 ms