Figure 1.

LPP-LTP is endocannabinoid and CB₁ dependent. A, The CB₁ inverse agonist AM251 (5 µm, at horizontal bar) disrupts LPP-LTP with or without PTX (10 µm) in the ACSF bath. Veh-treated slices included those tested with (+) and without (−) PTX present. Potentiation, assessed 55–60 min after high-frequency stimulation, was greatly reduced in both AM251 groups (p < 0.0004, −PTX; p < 0.001, +PTX; n = 5 each) relative to veh. B, Perfusion of the CB₁ antagonist SR141716A (5 µm) in the presence of 100 µm PTX significantly attenuated LPP-LTP, as assessed with field recordings (p = 0.0004, two-tailed t test for percentage of LTP in veh vs SR141716A). C, CB₁ antagonist SR141716A also significantly reduced the percentage of LPP potentiation as assessed 25 min postinduction using voltage-clamp recordings of granule cells in slices treated with veh (n = 8) or 25 µm SR141716A (n = 6; **p < 0.005, two-tailed t test vs veh+PTX): traces show EPSCs collected before and 30 min after induction for veh slices. Calibration: 100 pA, 50 ms. D, E, AM251 did not reduce LTP of the MPP (D) or the S-C afferents of field CA1 (E; n = 5/group). F, Relationship of the peak amplitude of the fiber volley to the fEPSP slope (input/output curves) in the outer molecular layer of the DG with LPP stimulation in WT and CB₁ KO mice: traces are averaged group responses after normalization of mean fEPSPs for individual slices to their peak amplitude. Group fEPSPs for WT and CB₁ KO slices were indistinguishable. G, LTP in the LPP was severely impaired in CB₁ KO mice (p < 0.0001; n = 10/group). H, LTP did not differ between CB₁ KOs and WTs in field CA1 (p = 0.89, t₍₁₀₎ = 0.16: n = 6/group). All panels show results from field recordings (fEPSPs), except for the bar graph in C, which shows the results of whole-cell, voltage-clamp recordings.