(a) Time-dependent effects of calpain inhibition on LTP. Hippocampal slices were prepared from adult rats and LTP was induced in field CA1 by TBS (black arrow). Vehicle or CI-III (10 μM) was applied for 10 min before and continued 5 min after TBS (cyan). Alternatively, CI-III (10 μM) was applied for 30 min starting 10 min (blue) or 60 min (magenta) post TBS. Slopes of field excitatory postsynaptic potentials (fEPSPs) are expressed as per cent of the average values recorded during the 10-min baseline (means±s.e.m. of five to ten slices from three to five animals). Basal synaptic transmission did not change during the recording period (red). (b) Representative traces for fEPSPs recorded at the indicated time points (1, 2 and 3) under different experimental conditions. Calibration: 0.5 mV per 5 ms. (c) Post-TBS calpain inhibition blocks TBS2-induced further potentiation. TBS was applied as indicated by arrows. CI-III (10 μM) was applied during the time indicated by the horizontal lines. A second TBS was delivered 60 min after the first TBS and fEPSP was recorded for an additional 40 min (means±s.e.m. of six to eight slices from three to four animals). (d) Top: CI-III (10 μM) was applied for 30 min starting 10 min after TBS1 (arrow). At the end of calpain inhibitor treatment, stimulation intensity was decreased to obtain a response equivalent to the pre-TBS value. After 20 min, TBS2 was delivered and responses recorded for an additional 40 min (representative experiment). Bottom: CI-III (10 μM) was applied to naive slices for 30 min. After 20 min, TBS was applied and responses recorded for an additional 40 min (representative experiment). (e) Comparison of the responses highlighted in d (means±s.e.m. of six to eight slices).