Figure 1.

Patterned low-frequency stimulation leads to potentiation of mossy fiber EPSCs. A, Mossy fiber EPSCs recorded from CA3 pyramidal neurons in mouse hippocampal slices were elicited at a basal frequency of 0.05 Hz and train frequency of 1 Hz (gray bar, 2 min). Paired-pulse ratios were monitored during the duration of the experiment, and mossy fiber activation was confirmed with administration of the group II mGlu receptor agonist DCG-IV. B, Stimuli were evoked at a 1 Hz frequency with single LFS (open circles) or with paired LFS with a 40 ms interstimulus interval (PP-LFS, gray squares). Mean normalized EPSC amplitudes show that mf-EPSCs returned to basal levels after single pulses were administered. In contrast, PP-LFS stimulation potentiated mf-EPSCs 30 min after train stimulation. Insets in this and other panels show representative mf-EPSCs during prestimulus control (a, black trace) and during the last 5 min of the recordings (b, gray trace). Calibration: x-axes, 10 ms; y-axes, 100 pA (single stimulation) and 150 pA (PP-LFS stimulation). C, Cumulative probability histogram for mean 1 Hz single LFS (open circles) and 1 Hz PP-LFS (gray squares). The dashed line indicates 100% control amplitude. D, Plot of the PPR during baseline and after mf-LFP induction in 1 Hz PP-LFS experiments. Gray boxes represent average PPR and SEM for pretrain control and 30 min posttrain. E, Mean normalized amplitudes of mf-EPSCs evoked singly (open circles) or in pairs (PP-LFS, gray squares) in experiments where the train frequency was 2 Hz (for 1 min). Single stimuli did not potentiate mf-EPSCs, whereas a PP-LFS paradigm effectively potentiated mean amplitudes. Calibration: x-axes, 10 ms; y-axes, 150 pA. F, Mean normalized mf-EPSC amplitudes were potentiated in 1 Hz PP-LFS experiments in which the extracellular divalent cation concentrations were raised to 4 mm Ca²⁺ and 4 mm Mg²⁺. Calibration: x-axis, 10 ms; y-axis, 250 pA. G, mf-LFP occurs at more physiological temperatures. Calibration: x-axis, 10 ms; y-axis, 250 pA. H, Recording mf-EPSCs for a longer experimental time course revealed that elevated amplitudes returned to control levels 1 h after PP-LFS induction. Inset traces in this case are taken from the baseline period (a, black) and 1 h after PP-LFS (b, gray; overlapping with the control trace). Calibration: x-axis, 10 ms; y-axis, 250 pA. I, Bar graph summarizing mf-LFP expressed as a percentage of control amplitudes within each experimental group. Asterisks represent significance of individual degrees of potentiation compared with baseline within each experimental group (*p < 0.05; **p < 0.01).