Fig. 6. Metaplastic inhibition of the late phase of long-term potentiation (L-LTP). (A) Transient depression was observed after 5 Hz low-frequency stimulation for 3 min (LFS) was applied to area CA1 of hippocampal slices from B6 mice. However, fEPSP slopes recovered within 7 min after the end of LFS (open circles). Sample fEPSP traces from one experiment are shown; these were recorded 15 min before (a), during (b), immediately after (c), and 20 min after (d) LFS. (B) Prior LFS at 5 Hz does not affect early LTP induced by a single 100 Hz train. Control slices (open squares) generated LTP that was similar in magnitude and time course to LTP induced in slices that received LFS prior to tetanization (solid circles). Inset: sample fEPSP traces from one experiment, measured 10 min before and 60 min after E-LTP induction. (C) Four successive trains of 100 Hz, spaced 5 min apart, induced robust L-LTP in control slices (open squares) and in slices that received a brief prior episode of LFS (5 Hz, 30 s; solid triangles). No L-LTP was seen in slices that received more prolonged LFS (5 Hz, 3 min; solid circles) prior to HFS. Inset: sample traces from an experiment, measured 10 min before (Control) and 2 h after L-LTP induction. (D) Increasing the time interval between LFS and L-LTP induction abolishes anterograde metaplasticity of L-LTP. Defective L-LTP was observed when LFS was applied 20 min before L-LTP induction (solid circles). By contrast, normal L-LTP was seen when the time interval between LFS and HFS was extended to 40 min (solid triangle). Adapted from (Woo and Nguyen, 2002). (Copyright 2002, Cold Spring Harbor Laboratory Press, used with permission.)